The Experts below are selected from a list of 759 Experts worldwide ranked by ideXlab platform

Jeffrey E Segall - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    CONTEXT: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. OBJECTIVE: To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. DESIGN: For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. RESULTS: Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. CONCLUSIONS: microRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

  • Abstract 185: microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer having an association with locoregional recurrence and lymph node metastasis. We previously reported that patients with lower microRNA-375 (miR-375) tumor:normal expression levels showed significantly decreased disease-specific survival, increased locoregional recurrence and distant metastasis. We also previously described that HNSCC cells with increased miR-375 showed significantly diminished invasion in vitro. The ability of cancer cells to degrade extracellular matrix (ECM) through secreted and membrane-bound proteases allows local invasion into the surrounding stroma, as well as possible metastasis. Invadopodia are specialized actin-rich structures, which mediate ECM degradation. Our objective was to determine whether elevated miR-375 expression in HNSCC cells also affects invadopodia formation and activity. For the evaluation of the matrix degradation properties of UMSCC1 and OSC19 cell lines, an invadopodial matrix degradation assay was used. Western blot analyses were conducted to measure the total protein levels of selected invadopodia-associated proteins. The tyrosine phosphorylation states of cortactin were evaluated by immunoprecipitation experiments. For the detection of levels of secreted proteases in the conditioned cell growth medium, Human Protease Arrays were used. Quantitative RT-PCR measurements were used to evaluate the mRNA expression levels of the commonly regulated proteases. We observed that the HNSCC cell lines with elevated miR-375 expression showed significant reductions in ECM degradation. We further identified that HNSCC cells expressing increased miR-375 expression had significantly suppressed amounts of mature invadopodia, although the levels of invadopodium precursors were not significantly altered. We determined that increased miR-375 expression in the HNSCC cell lines did not reduce cellular levels of invadopodia components, such as Tks5, cortactin and fascin. We also did not observe significant alterations to the tyrosine phosphorylation states of cortactin in the HNSCC cell lines. However, we found that the HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression and secreted levels of specific proteases, including Kallikrein 6, Kallikrein 10, and MMP-9. In summary, we have extended our understanding of the impact of miR-375 expression levels on HNSCC invasion. We demonstrated that increased miR-375 expression in HNSCC cells reduced ECM degradation and invadopodial activity. Our data suggest that reduced miR-375 expression in HNSCC patients can contribute to the invasive properties of head and neck cancer through increased invadopodial activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, John S. Condeelis, Thomas M. Harris, Thomas J. Ow, Michael B. Prystowsky, Geoffrey J. Childs, Jeffrey E. Segall. microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2015-185

  • microRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma.
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 185 microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 1452 microRNA 375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity
    Cancer Research, 2014
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Ruth Hogue Angeletti, Jeffrey E Segall
    Abstract:

    Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group previously reported that miR-375 expression levels correlate with patient survival, recurrence and distant metastasis. We have previously observed diminished HNSCC invasion in vitro correlates with increased miR-375 expression. To assess whether the miR-375 over-expressing transductant lines have reduced matrix degradation properties, a fluorescent matrix degradation assay was used. We have observed that miR-375 over-expression in HNSCC cells suppresses extracellular matrix degradation. We further determined whether miR-375 over-expressing cells show reduced invadopodium formation and maturation. We observed miR-375 expression in HNSCC cell lines reduces the number of mature invadopodia, but does not affect levels of invadopodium precursors. We examined the phosphorylation and total levels of key invadopodia components (Tks5 and cortactin) to determine whether changes in regulation or expression of these components may lead impaired matrix degradation properties. We determined that miR-375 expression in HNSCC cell lines does not reduce cellular levels of cortactin and Tks5, nor is tyrosine phosphorylation of cortactin altered. To identify candidate proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC). Candidate target proteins are being validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, increased miR-375 expression may suppress the invasive properties of HNSCC through diminished invadopodia activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, Jihyeon Lim, Ruth Angeletti, John Condeelis, Thomas Harris, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall. microRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1452. doi:10.1158/1538-7445.AM2014-1452

Lizandra Jimenez - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    CONTEXT: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. OBJECTIVE: To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. DESIGN: For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. RESULTS: Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. CONCLUSIONS: microRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

  • Abstract 185: microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer having an association with locoregional recurrence and lymph node metastasis. We previously reported that patients with lower microRNA-375 (miR-375) tumor:normal expression levels showed significantly decreased disease-specific survival, increased locoregional recurrence and distant metastasis. We also previously described that HNSCC cells with increased miR-375 showed significantly diminished invasion in vitro. The ability of cancer cells to degrade extracellular matrix (ECM) through secreted and membrane-bound proteases allows local invasion into the surrounding stroma, as well as possible metastasis. Invadopodia are specialized actin-rich structures, which mediate ECM degradation. Our objective was to determine whether elevated miR-375 expression in HNSCC cells also affects invadopodia formation and activity. For the evaluation of the matrix degradation properties of UMSCC1 and OSC19 cell lines, an invadopodial matrix degradation assay was used. Western blot analyses were conducted to measure the total protein levels of selected invadopodia-associated proteins. The tyrosine phosphorylation states of cortactin were evaluated by immunoprecipitation experiments. For the detection of levels of secreted proteases in the conditioned cell growth medium, Human Protease Arrays were used. Quantitative RT-PCR measurements were used to evaluate the mRNA expression levels of the commonly regulated proteases. We observed that the HNSCC cell lines with elevated miR-375 expression showed significant reductions in ECM degradation. We further identified that HNSCC cells expressing increased miR-375 expression had significantly suppressed amounts of mature invadopodia, although the levels of invadopodium precursors were not significantly altered. We determined that increased miR-375 expression in the HNSCC cell lines did not reduce cellular levels of invadopodia components, such as Tks5, cortactin and fascin. We also did not observe significant alterations to the tyrosine phosphorylation states of cortactin in the HNSCC cell lines. However, we found that the HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression and secreted levels of specific proteases, including Kallikrein 6, Kallikrein 10, and MMP-9. In summary, we have extended our understanding of the impact of miR-375 expression levels on HNSCC invasion. We demonstrated that increased miR-375 expression in HNSCC cells reduced ECM degradation and invadopodial activity. Our data suggest that reduced miR-375 expression in HNSCC patients can contribute to the invasive properties of head and neck cancer through increased invadopodial activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, John S. Condeelis, Thomas M. Harris, Thomas J. Ow, Michael B. Prystowsky, Geoffrey J. Childs, Jeffrey E. Segall. microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2015-185

  • microRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma.
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 185 microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 1452 microRNA 375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity
    Cancer Research, 2014
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Ruth Hogue Angeletti, Jeffrey E Segall
    Abstract:

    Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group previously reported that miR-375 expression levels correlate with patient survival, recurrence and distant metastasis. We have previously observed diminished HNSCC invasion in vitro correlates with increased miR-375 expression. To assess whether the miR-375 over-expressing transductant lines have reduced matrix degradation properties, a fluorescent matrix degradation assay was used. We have observed that miR-375 over-expression in HNSCC cells suppresses extracellular matrix degradation. We further determined whether miR-375 over-expressing cells show reduced invadopodium formation and maturation. We observed miR-375 expression in HNSCC cell lines reduces the number of mature invadopodia, but does not affect levels of invadopodium precursors. We examined the phosphorylation and total levels of key invadopodia components (Tks5 and cortactin) to determine whether changes in regulation or expression of these components may lead impaired matrix degradation properties. We determined that miR-375 expression in HNSCC cell lines does not reduce cellular levels of cortactin and Tks5, nor is tyrosine phosphorylation of cortactin altered. To identify candidate proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC). Candidate target proteins are being validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, increased miR-375 expression may suppress the invasive properties of HNSCC through diminished invadopodia activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, Jihyeon Lim, Ruth Angeletti, John Condeelis, Thomas Harris, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall. microRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1452. doi:10.1158/1538-7445.AM2014-1452

Soocheon Chae - One of the best experts on this subject based on the ideXlab platform.

  • reduced microRNA 375 in colorectal cancer upregulates metadherin mediated signaling
    World Journal of Gastroenterology, 2019
    Co-Authors: Jisu Mo, Woncheol Park, Soocheon Chae
    Abstract:

    BACKGROUND The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375.

  • microRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the ctgf egfr signaling pathway
    International Journal of Cancer, 2017
    Co-Authors: Khondoker Jahengir Alam, Jisu Mo, Woncheol Park, Soocheon Chae
    Abstract:

    microRNA 375 (MIR375) is significantly down regulated in human colorectal cancer (CRC) tissues; we have previously identified MIR375 as a colon cancer associated microRNA (miRNA). We identified putative MIR375 target genes by comparing the mRNA microarray analysis data of MIR375-overexpressing cells with the candidate MIR375 target genes predicted by public bioinformatic tools. We investigated that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human CRC tissues in comparison with the corresponding normal colon tissues. We demonstrated that the expression levels of molecules in EGFR signaling pathways were regulated by MIR375 in colorectal cells. Using immunohistochemistry and the xenograft of MIR375-overexpressing colorectal cells in mice, we showed that MIR375 regulates cell growth and proliferation, angiogenesis, cell migration, cell cycle arrest, apoptosis, and necrosis in colon cells. Furthermore, results of MIR375 overexpression and cetuximab treatment indicated that the apoptosis and necrosis in colon cells were synergistically enhanced. Our results suggest that the down-regulation of MIR375 modulates EGFR signaling pathways in human colorectal cells and tissues by increasing CTGF expression; therefore, MIR375 may have a therapeutic value in relation to human CRC.

  • microRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the CTGF-EGFR signaling pathway.
    International Journal of Cancer, 2017
    Co-Authors: Khondoker Jahengir Alam, Jisu Mo, Woncheol Park, Soocheon Chae
    Abstract:

    microRNA 375 (MIR375) is significantly down regulated in human colorectal cancer (CRC) tissues; we have previously identified MIR375 as a colon cancer associated microRNA (miRNA). We identified putative MIR375 target genes by comparing the mRNA microarray analysis data of MIR375-overexpressing cells with the candidate MIR375 target genes predicted by public bioinformatic tools. We investigated that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human CRC tissues in comparison with the corresponding normal colon tissues. We demonstrated that the expression levels of molecules in EGFR signaling pathways were regulated by MIR375 in colorectal cells. Using immunohistochemistry and the xenograft of MIR375-overexpressing colorectal cells in mice, we showed that MIR375 regulates cell growth and proliferation, angiogenesis, cell migration, cell cycle arrest, apoptosis, and necrosis in colon cells. Furthermore, results of MIR375 overexpression and cetuximab treatment indicated that the apoptosis and necrosis in colon cells were synergistically enhanced. Our results suggest that the down-regulation of MIR375 modulates EGFR signaling pathways in human colorectal cells and tissues by increasing CTGF expression; therefore, MIR375 may have a therapeutic value in relation to human CRC. This article is protected by copyright. All rights reserved.

Thomas M Harris - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    CONTEXT: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. OBJECTIVE: To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. DESIGN: For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. RESULTS: Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. CONCLUSIONS: microRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

  • Abstract 185: microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer having an association with locoregional recurrence and lymph node metastasis. We previously reported that patients with lower microRNA-375 (miR-375) tumor:normal expression levels showed significantly decreased disease-specific survival, increased locoregional recurrence and distant metastasis. We also previously described that HNSCC cells with increased miR-375 showed significantly diminished invasion in vitro. The ability of cancer cells to degrade extracellular matrix (ECM) through secreted and membrane-bound proteases allows local invasion into the surrounding stroma, as well as possible metastasis. Invadopodia are specialized actin-rich structures, which mediate ECM degradation. Our objective was to determine whether elevated miR-375 expression in HNSCC cells also affects invadopodia formation and activity. For the evaluation of the matrix degradation properties of UMSCC1 and OSC19 cell lines, an invadopodial matrix degradation assay was used. Western blot analyses were conducted to measure the total protein levels of selected invadopodia-associated proteins. The tyrosine phosphorylation states of cortactin were evaluated by immunoprecipitation experiments. For the detection of levels of secreted proteases in the conditioned cell growth medium, Human Protease Arrays were used. Quantitative RT-PCR measurements were used to evaluate the mRNA expression levels of the commonly regulated proteases. We observed that the HNSCC cell lines with elevated miR-375 expression showed significant reductions in ECM degradation. We further identified that HNSCC cells expressing increased miR-375 expression had significantly suppressed amounts of mature invadopodia, although the levels of invadopodium precursors were not significantly altered. We determined that increased miR-375 expression in the HNSCC cell lines did not reduce cellular levels of invadopodia components, such as Tks5, cortactin and fascin. We also did not observe significant alterations to the tyrosine phosphorylation states of cortactin in the HNSCC cell lines. However, we found that the HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression and secreted levels of specific proteases, including Kallikrein 6, Kallikrein 10, and MMP-9. In summary, we have extended our understanding of the impact of miR-375 expression levels on HNSCC invasion. We demonstrated that increased miR-375 expression in HNSCC cells reduced ECM degradation and invadopodial activity. Our data suggest that reduced miR-375 expression in HNSCC patients can contribute to the invasive properties of head and neck cancer through increased invadopodial activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, John S. Condeelis, Thomas M. Harris, Thomas J. Ow, Michael B. Prystowsky, Geoffrey J. Childs, Jeffrey E. Segall. microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2015-185

  • microRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma.
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 185 microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 1452 microRNA 375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity
    Cancer Research, 2014
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Ruth Hogue Angeletti, Jeffrey E Segall
    Abstract:

    Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group previously reported that miR-375 expression levels correlate with patient survival, recurrence and distant metastasis. We have previously observed diminished HNSCC invasion in vitro correlates with increased miR-375 expression. To assess whether the miR-375 over-expressing transductant lines have reduced matrix degradation properties, a fluorescent matrix degradation assay was used. We have observed that miR-375 over-expression in HNSCC cells suppresses extracellular matrix degradation. We further determined whether miR-375 over-expressing cells show reduced invadopodium formation and maturation. We observed miR-375 expression in HNSCC cell lines reduces the number of mature invadopodia, but does not affect levels of invadopodium precursors. We examined the phosphorylation and total levels of key invadopodia components (Tks5 and cortactin) to determine whether changes in regulation or expression of these components may lead impaired matrix degradation properties. We determined that miR-375 expression in HNSCC cell lines does not reduce cellular levels of cortactin and Tks5, nor is tyrosine phosphorylation of cortactin altered. To identify candidate proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC). Candidate target proteins are being validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, increased miR-375 expression may suppress the invasive properties of HNSCC through diminished invadopodia activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, Jihyeon Lim, Ruth Angeletti, John Condeelis, Thomas Harris, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall. microRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1452. doi:10.1158/1538-7445.AM2014-1452

Michael B Prystowsky - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    CONTEXT: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. OBJECTIVE: To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. DESIGN: For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. RESULTS: Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. CONCLUSIONS: microRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

  • Abstract 185: microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer having an association with locoregional recurrence and lymph node metastasis. We previously reported that patients with lower microRNA-375 (miR-375) tumor:normal expression levels showed significantly decreased disease-specific survival, increased locoregional recurrence and distant metastasis. We also previously described that HNSCC cells with increased miR-375 showed significantly diminished invasion in vitro. The ability of cancer cells to degrade extracellular matrix (ECM) through secreted and membrane-bound proteases allows local invasion into the surrounding stroma, as well as possible metastasis. Invadopodia are specialized actin-rich structures, which mediate ECM degradation. Our objective was to determine whether elevated miR-375 expression in HNSCC cells also affects invadopodia formation and activity. For the evaluation of the matrix degradation properties of UMSCC1 and OSC19 cell lines, an invadopodial matrix degradation assay was used. Western blot analyses were conducted to measure the total protein levels of selected invadopodia-associated proteins. The tyrosine phosphorylation states of cortactin were evaluated by immunoprecipitation experiments. For the detection of levels of secreted proteases in the conditioned cell growth medium, Human Protease Arrays were used. Quantitative RT-PCR measurements were used to evaluate the mRNA expression levels of the commonly regulated proteases. We observed that the HNSCC cell lines with elevated miR-375 expression showed significant reductions in ECM degradation. We further identified that HNSCC cells expressing increased miR-375 expression had significantly suppressed amounts of mature invadopodia, although the levels of invadopodium precursors were not significantly altered. We determined that increased miR-375 expression in the HNSCC cell lines did not reduce cellular levels of invadopodia components, such as Tks5, cortactin and fascin. We also did not observe significant alterations to the tyrosine phosphorylation states of cortactin in the HNSCC cell lines. However, we found that the HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression and secreted levels of specific proteases, including Kallikrein 6, Kallikrein 10, and MMP-9. In summary, we have extended our understanding of the impact of miR-375 expression levels on HNSCC invasion. We demonstrated that increased miR-375 expression in HNSCC cells reduced ECM degradation and invadopodial activity. Our data suggest that reduced miR-375 expression in HNSCC patients can contribute to the invasive properties of head and neck cancer through increased invadopodial activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, John S. Condeelis, Thomas M. Harris, Thomas J. Ow, Michael B. Prystowsky, Geoffrey J. Childs, Jeffrey E. Segall. microRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2015-185

  • microRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma.
    Archives of Pathology & Laboratory Medicine, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey J. Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 185 microRNA 375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma
    Cancer Research, 2015
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Thomas J Ow, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall
    Abstract:

    Context.— Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.— To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.— For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of...

  • abstract 1452 microRNA 375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity
    Cancer Research, 2014
    Co-Authors: Lizandra Jimenez, Ved P Sharma, John S Condeelis, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Ruth Hogue Angeletti, Jeffrey E Segall
    Abstract:

    Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group previously reported that miR-375 expression levels correlate with patient survival, recurrence and distant metastasis. We have previously observed diminished HNSCC invasion in vitro correlates with increased miR-375 expression. To assess whether the miR-375 over-expressing transductant lines have reduced matrix degradation properties, a fluorescent matrix degradation assay was used. We have observed that miR-375 over-expression in HNSCC cells suppresses extracellular matrix degradation. We further determined whether miR-375 over-expressing cells show reduced invadopodium formation and maturation. We observed miR-375 expression in HNSCC cell lines reduces the number of mature invadopodia, but does not affect levels of invadopodium precursors. We examined the phosphorylation and total levels of key invadopodia components (Tks5 and cortactin) to determine whether changes in regulation or expression of these components may lead impaired matrix degradation properties. We determined that miR-375 expression in HNSCC cell lines does not reduce cellular levels of cortactin and Tks5, nor is tyrosine phosphorylation of cortactin altered. To identify candidate proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC). Candidate target proteins are being validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, increased miR-375 expression may suppress the invasive properties of HNSCC through diminished invadopodia activity. Citation Format: Lizandra Jimenez, Ved P. Sharma, Jihyeon Lim, Ruth Angeletti, John Condeelis, Thomas Harris, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall. microRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1452. doi:10.1158/1538-7445.AM2014-1452