The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
P K Marcom - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy enriches for an invasive triple negative breast tumor Cell Subpopulation expressing a precursor form of n cadherin on the Cell surface
Oncotarget, 2016Co-Authors: Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle L Bowie, Edgardo Parillacastellar, Gustaaf G De Ridder, P K MarcomAbstract:// Erik R. Nelson 1,5 , Shenduo Li 4 , Margaret Kennedy 4 , Sturgis Payne 4 , Kelly Kilibarda 4 , Jeffrey Groth 4 , Michelle Bowie 4 , Edgardo Parilla-Castellar 4 , Gustaaf de Ridder 4 , Paul Kelly Marcom 4 , Matthew Lyes 4 , Bercedis L. Peterson 2 , Michael Cook 3 , Salvatore V. Pizzo 4 , Donald P. McDonnell 5 and Robin E. Bachelder 4 1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana Champaign, Urbana and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, USA 2 Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA 3 Department of Immunology, Duke University School of Medicine, Durham, NC, USA 4 Department of Pathology, Duke University Medical Center, Durham, NC, USA 5 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA Correspondence to: Robin E. Bachelder, email: // Keywords : Precursor-N-cadherin, triple-negative breast cancer, invasion, metastasis, chemotherapy resistance Received : August 16, 2016 Accepted : October 07, 2016 Published : October 28, 2016 Abstract Background: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor Cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others’ indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor Cell Subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC. Methods: The invasive behavior of TNBC tumor Cells surviving short-term chemotherapy treatment in vitro was studied using transwell invasion assays and an experimental metastasis model. mRNA expression levels of neural cadherin (N-cadherin), an adhesion molecule that promotes invasion, was assessed by PCR. Expression of N-cadherin and its precursor form (pro-N-cadherin) was assessed by immunoblotting and flow cytometry. Pro-N-cadherin immunohistochemistry was performed on tumors obtained from patients pre- and post- neoadjuvant chemotherapy treatment. Results: TNBC Cells surviving short-term chemotherapy treatment exhibited increased invasive behavior and capacity to colonize metastatic sites compared to untreated tumor Cells. The invasive behavior of chemo-resistant Cells was associated with their increased Cell surface expression of precursor N-cadherin (pro-N-cadherin). An antibody specific for the precursor domain of N-cadherin inhibited invasion of chemo-resistant TNBC Cells. To begin to validate our findings in humans, we showed that the percent Cell surface pro-N-cadherin (+) tumor Cells increased in patients post- chemotherapy treatment. Conclusions: TNBC Cells surviving short-term chemotherapy treatment are more invasive than bulk tumor Cells. Cell surface pro-N-cadherin expression is associated with the invasive and chemo-resistant behaviors of this tumor Cell subset. Our findings indicate the importance of future studies determining the value of Cell surface pro-N-cadherin as: 1) a biomarker for TNBC recurrence and 2) a therapeutic target for eliminating chemo-residual disease.
Baijun Dong - One of the best experts on this subject based on the ideXlab platform.
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identification of a zeb1 expressing basal stem Cell Subpopulation in the prostate
Nature Communications, 2020Co-Authors: Xue Wang, Haibo Xu, Chaping Cheng, Zhongzhong Ji, Huifang Zhao, Yaru Sheng, Xiaoxia Li, J Wang, Y He, Baijun DongAbstract:The basal Cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem Cells. However, basal Cells are heterogenous and the stem Cell Subpopulation within basal Cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal Cell Subpopulation. The Zeb1+ prostate epithelial Cells are multipotent prostate basal stem Cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-Cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal Cell development. Utilizing unbiased single-Cell transcriptomic analysis of over 9000 mouse prostate basal Cells, we confirm the existence of the Zeb1+ basal Cell subset. Moreover, Zeb1+ epithelial Cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis. Heterogeneous populations of basal Cells in the prostate epithelium contain stem Cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem Cells that self-renew, generate prostate glandular structures with all 3 epithelial Cell types and are required for prostate basal Cell development.
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identification of a basal stem Cell Subpopulation in the prostate via functional lineage tracing and single Cell rna seq analyses
bioRxiv, 2019Co-Authors: Xue Wang, Haibo Xu, Chaping Cheng, Zhongzhong Ji, Huifang Zhao, Yaru Sheng, Xiaoxia Li, J Wang, Y He, Baijun DongAbstract:The basal Cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem Cells. However, basal Cells are heterogenous and the stem Cell Subpopulation within basal Cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal Cell Subpopulation based on both immunocytochemical and Cell lineage tracing analysis. The Zeb1+ prostate epithelial Cells are multipotent prostate basal stem Cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial Cell types at the single-Cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal Cell development. Utilizing unbiased single Cell transcriptomic analysis of over 9000 mouse prostate basal Cells, we find that Zeb1+ basal Cell subset shares gene expression signatures with both epithelial and mesenchymal Cells and stands out uniquely among all the basal Cell clusters. Moreover, Zeb1+ epithelial Cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis. Key words: prostate basal stem Cells, Zeb1, lineage tracing, single-Cell RNA sequencing, Wnt signaling pathway, prostate cancer, tumor initiating Cell,
Erik R Nelson - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy enriches for an invasive triple negative breast tumor Cell Subpopulation expressing a precursor form of n cadherin on the Cell surface
Oncotarget, 2016Co-Authors: Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle L Bowie, Edgardo Parillacastellar, Gustaaf G De Ridder, P K MarcomAbstract:// Erik R. Nelson 1,5 , Shenduo Li 4 , Margaret Kennedy 4 , Sturgis Payne 4 , Kelly Kilibarda 4 , Jeffrey Groth 4 , Michelle Bowie 4 , Edgardo Parilla-Castellar 4 , Gustaaf de Ridder 4 , Paul Kelly Marcom 4 , Matthew Lyes 4 , Bercedis L. Peterson 2 , Michael Cook 3 , Salvatore V. Pizzo 4 , Donald P. McDonnell 5 and Robin E. Bachelder 4 1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana Champaign, Urbana and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, USA 2 Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA 3 Department of Immunology, Duke University School of Medicine, Durham, NC, USA 4 Department of Pathology, Duke University Medical Center, Durham, NC, USA 5 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA Correspondence to: Robin E. Bachelder, email: // Keywords : Precursor-N-cadherin, triple-negative breast cancer, invasion, metastasis, chemotherapy resistance Received : August 16, 2016 Accepted : October 07, 2016 Published : October 28, 2016 Abstract Background: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor Cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others’ indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor Cell Subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC. Methods: The invasive behavior of TNBC tumor Cells surviving short-term chemotherapy treatment in vitro was studied using transwell invasion assays and an experimental metastasis model. mRNA expression levels of neural cadherin (N-cadherin), an adhesion molecule that promotes invasion, was assessed by PCR. Expression of N-cadherin and its precursor form (pro-N-cadherin) was assessed by immunoblotting and flow cytometry. Pro-N-cadherin immunohistochemistry was performed on tumors obtained from patients pre- and post- neoadjuvant chemotherapy treatment. Results: TNBC Cells surviving short-term chemotherapy treatment exhibited increased invasive behavior and capacity to colonize metastatic sites compared to untreated tumor Cells. The invasive behavior of chemo-resistant Cells was associated with their increased Cell surface expression of precursor N-cadherin (pro-N-cadherin). An antibody specific for the precursor domain of N-cadherin inhibited invasion of chemo-resistant TNBC Cells. To begin to validate our findings in humans, we showed that the percent Cell surface pro-N-cadherin (+) tumor Cells increased in patients post- chemotherapy treatment. Conclusions: TNBC Cells surviving short-term chemotherapy treatment are more invasive than bulk tumor Cells. Cell surface pro-N-cadherin expression is associated with the invasive and chemo-resistant behaviors of this tumor Cell subset. Our findings indicate the importance of future studies determining the value of Cell surface pro-N-cadherin as: 1) a biomarker for TNBC recurrence and 2) a therapeutic target for eliminating chemo-residual disease.
Owen N Witte - One of the best experts on this subject based on the ideXlab platform.
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pten deletion leads to the expansion of a prostatic stem progenitor Cell Subpopulation and tumor initiation
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Shunyou Wang, Alejandro J Garcia, Michelle Wu, Devon A Lawson, Owen N Witte, Hong WuAbstract:PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined Cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal Cell proliferation without blocking differentiation. Concomitant with basal Cell proliferation is the expansion of a prostate stem/progenitor-like Subpopulation as evidenced by the progressive increase of stem Cell antigen-1 (Sca-1)- and BCL-2-positive Cells. This observation provides strong evidence that basal Cell proliferation can be an initiating event for precancerous lesions. Sca-1+ and BCL-2+ progenitors may serve as cancer-initiating Cells in this model.
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the sca 1 Cell surface marker enriches for a prostate regenerating Cell Subpopulation that can initiate prostate tumorigenesis
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Devon A Lawson, Owen N WitteAbstract:Sca-1 (stem Cell antigen-1) enriches for murine prostate Cells capable of regenerating tubular structures containing basal and luminal Cell lineages in a dissociated Cell prostate regeneration system. Sca-1+ fractions are enriched for Cells at the G0 stage of the Cell cycle, and Sca-1+ Cells cluster in the proximal region of prostatic tubules where replication-quiescent Cells have been localized. Castration-induced enrichment for androgen-independent Cells results in a concomitant enrichment for Sca-1+ Cells. Genetic perturbations of PTEN/AKT signaling in prostate-regenerating Cells leads to the initiation of tumorigenesis, and cancer progression is associated with a dramatic increase in Sca-1+ Cells. Sca-1-enriched prostate-regenerating Cells possess multiple stem/progenitor Cell properties and can serve as targets for cancer initiation.
Devon A Lawson - One of the best experts on this subject based on the ideXlab platform.
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pten deletion leads to the expansion of a prostatic stem progenitor Cell Subpopulation and tumor initiation
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Shunyou Wang, Alejandro J Garcia, Michelle Wu, Devon A Lawson, Owen N Witte, Hong WuAbstract:PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined Cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal Cell proliferation without blocking differentiation. Concomitant with basal Cell proliferation is the expansion of a prostate stem/progenitor-like Subpopulation as evidenced by the progressive increase of stem Cell antigen-1 (Sca-1)- and BCL-2-positive Cells. This observation provides strong evidence that basal Cell proliferation can be an initiating event for precancerous lesions. Sca-1+ and BCL-2+ progenitors may serve as cancer-initiating Cells in this model.
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the sca 1 Cell surface marker enriches for a prostate regenerating Cell Subpopulation that can initiate prostate tumorigenesis
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Devon A Lawson, Owen N WitteAbstract:Sca-1 (stem Cell antigen-1) enriches for murine prostate Cells capable of regenerating tubular structures containing basal and luminal Cell lineages in a dissociated Cell prostate regeneration system. Sca-1+ fractions are enriched for Cells at the G0 stage of the Cell cycle, and Sca-1+ Cells cluster in the proximal region of prostatic tubules where replication-quiescent Cells have been localized. Castration-induced enrichment for androgen-independent Cells results in a concomitant enrichment for Sca-1+ Cells. Genetic perturbations of PTEN/AKT signaling in prostate-regenerating Cells leads to the initiation of tumorigenesis, and cancer progression is associated with a dramatic increase in Sca-1+ Cells. Sca-1-enriched prostate-regenerating Cells possess multiple stem/progenitor Cell properties and can serve as targets for cancer initiation.