The Experts below are selected from a list of 1443 Experts worldwide ranked by ideXlab platform
Harini Krishnan - One of the best experts on this subject based on the ideXlab platform.
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Podoplanin: An emerging cancer biomarker and therapeutic target.
Cancer Science, 2018Co-Authors: Harini Krishnan, Genichiro Ishii, Edward P Retzbach, Julie Rayes, Tomoyuki Miyashita, Stephanie A. Sheehan, Ai Takemoto, Yao‐wen Chang, Kazue Yoneda, Jun AsaiAbstract:: Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.
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abstract 4375 podoplanin PDPN novel biomarker and chemotherapeutic target
Cancer Research, 2015Co-Authors: Harini Krishnan, Maria I Ramirez, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, David Kephart, Angels T P Nguyen, Nimish K Acharya, Robert G Nagele, Todd W MillerAbstract:Cancer is a leading cause of death. In fact, cancer killed over 8 million people around the world in 2012. Over 90% of these cancer deaths are due to metastasis, which results from tumor cell migration and invasion. Specific cancer biomarkers need to be identified in order to effectively target these motile cells. The transmembrane glycoprotein receptor podoplanin (PDPN) promotes tumor cell motility and metastasis in many aggressive cancers. Indeed, PDPN has emerged as a prime cancer biomarker and chemotherapeutic target. Here, we describe how PDPN can be targeted to inhibit the growth and motility of melanoma and oral cancer cells. PDPN has a short intracellular domain of 9 amino acids which include two conserved serine residues. PDPN also has a large extracellular domain that is extensively O-glycosylated with α2,3-sialic acid linked to galactose. We are developing novel methods to target the intracellular and extracellular domains of PDPN to combat cancer progression. For example, we have found that some activators of protein kinase A can induce phosphorylation of the intracellular serine residues of PDPN to inhibit tumor cell migration. In addition, we have found that Maackia amurensis seed lectin (MASL) can target the extracellular domain of PDPN to inhibit tumor cell growth, migration, and tumor progression in cell culture and animal models. Furthermore, we utilized live cell imaging to find that PDPN expression can be modulated in cancer associated fibroblasts to inhibit neighboring tumor cell migration and survival. Thus, reagents can be used to target PDPN from inside of the cell and outside of the cell to inhibit tumor cell migration and combat cancer progression. This work illuminates novel strategies designed to exploit PDPN as a functionally relevant biomarker and chemotherapeutic target. Citation Format: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg. Podoplanin (PDPN): novel biomarker and chemotherapeutic target. [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 4375. doi:10.1158/1538-7445.AM2015-4375
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pka and cdk5 can phosphorylate specific serines on the intracellular domain of podoplanin PDPN to inhibit cell motility
Experimental Cell Research, 2015Co-Authors: Harini Krishnan, Edward P Retzbach, Maria I Ramirez, Hong Li, Todd W Miller, Gary S GoldbergAbstract:Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell migration, invasion, and cancer metastasis. In fact, PDPN expression is induced in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine residues that are conserved between species ranging from mouse to humans. Recent studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to inhibit cell migration. However, the number and identification of specific residues phosphorylated by PKA have not been defined. In addition, roles of other kinases that may phosphorylate PDPN to control cell migration have not been investigated. We report here that cyclin dependent kinase 5 (CDK5) can phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine residues to decrease cell motility. These results provide new insight into PDPN phosphorylation dynamics and the role of PDPN in cell motility. Understanding novel mechanisms of PDPN intracellular signaling could assist with designing novel targeted chemotherapeutic agents and procedures.
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Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
Oncotarget, 2015Co-Authors: Jhon A. Ochoa-alvarez, Harini Krishnan, Edward P Retzbach, John G. Pastorino, Evan Nevel, David J. Kephart, Yongquan Shen, Mahnaz Fatahzadeh, Soly BaredesAbstract:Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.
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Podoplanin: a marker for reactive gliosis in gliomas and brain injury.
Journal of Neuropathology and Experimental Neurology, 2015Co-Authors: Kushal Kolar, Harini Krishnan, Gary S Goldberg, Moises Freitas-andrade, John F. Bechberger, Christian C. NausAbstract:Abstract Reactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic protein-positive astrocytes within and adjacent to gliomas. The expression of PDPN in tumor-associated reactive astrocytes was confirmed by its colocalization with the astrocytic marker S100β and with connexin43, a major astrocytic gap junction protein. To determine whether the increase in PDPN is a general feature of gliosis, we used 2 mouse models in which astrogliosis was induced either by a needle injury or ischemia and observed similar upregulation of PDPN in reactive astrocytes in both models. Astrocytic PDPN was also found to be coexpressed with nestin, an intermediate filament marker for neural stem/progenitor cells. Our findings confirm that expression of PDPN is part of the normal host response to brain injury and gliomas, and suggest that it may be a novel cell surface marker for a specific population of reactive astrocytes in the vicinity of gliomas and nonneoplastic brain lesions. The findings also highlight the heterogeneity of glial fibrillary acidic protein-positive astrocytes in reactive gliosis.
Gary S Goldberg - One of the best experts on this subject based on the ideXlab platform.
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pka and cdk5 can phosphorylate specific serines on the intracellular domain of podoplanin PDPN to inhibit cell motility
Experimental Cell Research, 2015Co-Authors: Harini Krishnan, Edward P Retzbach, Maria I Ramirez, Hong Li, Todd W Miller, Gary S GoldbergAbstract:Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell migration, invasion, and cancer metastasis. In fact, PDPN expression is induced in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine residues that are conserved between species ranging from mouse to humans. Recent studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to inhibit cell migration. However, the number and identification of specific residues phosphorylated by PKA have not been defined. In addition, roles of other kinases that may phosphorylate PDPN to control cell migration have not been investigated. We report here that cyclin dependent kinase 5 (CDK5) can phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine residues to decrease cell motility. These results provide new insight into PDPN phosphorylation dynamics and the role of PDPN in cell motility. Understanding novel mechanisms of PDPN intracellular signaling could assist with designing novel targeted chemotherapeutic agents and procedures.
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Podoplanin: a marker for reactive gliosis in gliomas and brain injury.
Journal of Neuropathology and Experimental Neurology, 2015Co-Authors: Kushal Kolar, Harini Krishnan, Gary S Goldberg, Moises Freitas-andrade, John F. Bechberger, Christian C. NausAbstract:Abstract Reactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic protein-positive astrocytes within and adjacent to gliomas. The expression of PDPN in tumor-associated reactive astrocytes was confirmed by its colocalization with the astrocytic marker S100β and with connexin43, a major astrocytic gap junction protein. To determine whether the increase in PDPN is a general feature of gliosis, we used 2 mouse models in which astrogliosis was induced either by a needle injury or ischemia and observed similar upregulation of PDPN in reactive astrocytes in both models. Astrocytic PDPN was also found to be coexpressed with nestin, an intermediate filament marker for neural stem/progenitor cells. Our findings confirm that expression of PDPN is part of the normal host response to brain injury and gliomas, and suggest that it may be a novel cell surface marker for a specific population of reactive astrocytes in the vicinity of gliomas and nonneoplastic brain lesions. The findings also highlight the heterogeneity of glial fibrillary acidic protein-positive astrocytes in reactive gliosis.
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serines in the intracellular tail of podoplanin PDPN regulate cell motility
Journal of Biological Chemistry, 2013Co-Authors: Harini Krishnan, Maria I Ramirez, Todd W Miller, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, Meenakshi Lakshminarayanan, Mary C Williams, Gary S GoldbergAbstract:Abstract Podoplanin (PDPN) is a transmembrane receptor that affects the activities of Rho, ezrin, and other proteins to promote tumor cell motility, invasion, and metastasis. PDPN is found in many types of cancer and may serve as a tumor biomarker and chemotherapeutic target. The intracellular region of PDPN contains only two serines, and these are conserved in mammals including mice and humans. We generated cells from the embryos of homozygous null PDPN knock-out mice to investigate the relevance of these serines to cell growth and migration on a clear (PDPN-free) background. We report here that one or both of these serines can be phosphorylated by PKA (protein kinase A). We also report that conversion of these serines to nonphosphorylatable alanine residues enhances cell migration, whereas their conversion to phosphomimetic aspartate residues decreases cell migration. These results indicate that PKA can phosphorylate PDPN to decrease cell migration. In addition, we report that PDPN expression in fibroblasts causes them to facilitate the motility and viability of neighboring melanoma cells in coculture. These findings shed new light on how PDPN promotes cell motility, its role in tumorigenesis, and its utility as a functionally relevant biomarker and chemotherapeutic target.
Todd W Miller - One of the best experts on this subject based on the ideXlab platform.
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abstract 4375 podoplanin PDPN novel biomarker and chemotherapeutic target
Cancer Research, 2015Co-Authors: Harini Krishnan, Maria I Ramirez, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, David Kephart, Angels T P Nguyen, Nimish K Acharya, Robert G Nagele, Todd W MillerAbstract:Cancer is a leading cause of death. In fact, cancer killed over 8 million people around the world in 2012. Over 90% of these cancer deaths are due to metastasis, which results from tumor cell migration and invasion. Specific cancer biomarkers need to be identified in order to effectively target these motile cells. The transmembrane glycoprotein receptor podoplanin (PDPN) promotes tumor cell motility and metastasis in many aggressive cancers. Indeed, PDPN has emerged as a prime cancer biomarker and chemotherapeutic target. Here, we describe how PDPN can be targeted to inhibit the growth and motility of melanoma and oral cancer cells. PDPN has a short intracellular domain of 9 amino acids which include two conserved serine residues. PDPN also has a large extracellular domain that is extensively O-glycosylated with α2,3-sialic acid linked to galactose. We are developing novel methods to target the intracellular and extracellular domains of PDPN to combat cancer progression. For example, we have found that some activators of protein kinase A can induce phosphorylation of the intracellular serine residues of PDPN to inhibit tumor cell migration. In addition, we have found that Maackia amurensis seed lectin (MASL) can target the extracellular domain of PDPN to inhibit tumor cell growth, migration, and tumor progression in cell culture and animal models. Furthermore, we utilized live cell imaging to find that PDPN expression can be modulated in cancer associated fibroblasts to inhibit neighboring tumor cell migration and survival. Thus, reagents can be used to target PDPN from inside of the cell and outside of the cell to inhibit tumor cell migration and combat cancer progression. This work illuminates novel strategies designed to exploit PDPN as a functionally relevant biomarker and chemotherapeutic target. Citation Format: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg. Podoplanin (PDPN): novel biomarker and chemotherapeutic target. [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 4375. doi:10.1158/1538-7445.AM2015-4375
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pka and cdk5 can phosphorylate specific serines on the intracellular domain of podoplanin PDPN to inhibit cell motility
Experimental Cell Research, 2015Co-Authors: Harini Krishnan, Edward P Retzbach, Maria I Ramirez, Hong Li, Todd W Miller, Gary S GoldbergAbstract:Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell migration, invasion, and cancer metastasis. In fact, PDPN expression is induced in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine residues that are conserved between species ranging from mouse to humans. Recent studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to inhibit cell migration. However, the number and identification of specific residues phosphorylated by PKA have not been defined. In addition, roles of other kinases that may phosphorylate PDPN to control cell migration have not been investigated. We report here that cyclin dependent kinase 5 (CDK5) can phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine residues to decrease cell motility. These results provide new insight into PDPN phosphorylation dynamics and the role of PDPN in cell motility. Understanding novel mechanisms of PDPN intracellular signaling could assist with designing novel targeted chemotherapeutic agents and procedures.
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serines in the intracellular tail of podoplanin PDPN regulate cell motility
Journal of Biological Chemistry, 2013Co-Authors: Harini Krishnan, Maria I Ramirez, Todd W Miller, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, Meenakshi Lakshminarayanan, Mary C Williams, Gary S GoldbergAbstract:Abstract Podoplanin (PDPN) is a transmembrane receptor that affects the activities of Rho, ezrin, and other proteins to promote tumor cell motility, invasion, and metastasis. PDPN is found in many types of cancer and may serve as a tumor biomarker and chemotherapeutic target. The intracellular region of PDPN contains only two serines, and these are conserved in mammals including mice and humans. We generated cells from the embryos of homozygous null PDPN knock-out mice to investigate the relevance of these serines to cell growth and migration on a clear (PDPN-free) background. We report here that one or both of these serines can be phosphorylated by PKA (protein kinase A). We also report that conversion of these serines to nonphosphorylatable alanine residues enhances cell migration, whereas their conversion to phosphomimetic aspartate residues decreases cell migration. These results indicate that PKA can phosphorylate PDPN to decrease cell migration. In addition, we report that PDPN expression in fibroblasts causes them to facilitate the motility and viability of neighboring melanoma cells in coculture. These findings shed new light on how PDPN promotes cell motility, its role in tumorigenesis, and its utility as a functionally relevant biomarker and chemotherapeutic target.
Maria I Ramirez - One of the best experts on this subject based on the ideXlab platform.
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abstract 4375 podoplanin PDPN novel biomarker and chemotherapeutic target
Cancer Research, 2015Co-Authors: Harini Krishnan, Maria I Ramirez, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, David Kephart, Angels T P Nguyen, Nimish K Acharya, Robert G Nagele, Todd W MillerAbstract:Cancer is a leading cause of death. In fact, cancer killed over 8 million people around the world in 2012. Over 90% of these cancer deaths are due to metastasis, which results from tumor cell migration and invasion. Specific cancer biomarkers need to be identified in order to effectively target these motile cells. The transmembrane glycoprotein receptor podoplanin (PDPN) promotes tumor cell motility and metastasis in many aggressive cancers. Indeed, PDPN has emerged as a prime cancer biomarker and chemotherapeutic target. Here, we describe how PDPN can be targeted to inhibit the growth and motility of melanoma and oral cancer cells. PDPN has a short intracellular domain of 9 amino acids which include two conserved serine residues. PDPN also has a large extracellular domain that is extensively O-glycosylated with α2,3-sialic acid linked to galactose. We are developing novel methods to target the intracellular and extracellular domains of PDPN to combat cancer progression. For example, we have found that some activators of protein kinase A can induce phosphorylation of the intracellular serine residues of PDPN to inhibit tumor cell migration. In addition, we have found that Maackia amurensis seed lectin (MASL) can target the extracellular domain of PDPN to inhibit tumor cell growth, migration, and tumor progression in cell culture and animal models. Furthermore, we utilized live cell imaging to find that PDPN expression can be modulated in cancer associated fibroblasts to inhibit neighboring tumor cell migration and survival. Thus, reagents can be used to target PDPN from inside of the cell and outside of the cell to inhibit tumor cell migration and combat cancer progression. This work illuminates novel strategies designed to exploit PDPN as a functionally relevant biomarker and chemotherapeutic target. Citation Format: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg. Podoplanin (PDPN): novel biomarker and chemotherapeutic target. [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 4375. doi:10.1158/1538-7445.AM2015-4375
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pka and cdk5 can phosphorylate specific serines on the intracellular domain of podoplanin PDPN to inhibit cell motility
Experimental Cell Research, 2015Co-Authors: Harini Krishnan, Edward P Retzbach, Maria I Ramirez, Hong Li, Todd W Miller, Gary S GoldbergAbstract:Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell migration, invasion, and cancer metastasis. In fact, PDPN expression is induced in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine residues that are conserved between species ranging from mouse to humans. Recent studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to inhibit cell migration. However, the number and identification of specific residues phosphorylated by PKA have not been defined. In addition, roles of other kinases that may phosphorylate PDPN to control cell migration have not been investigated. We report here that cyclin dependent kinase 5 (CDK5) can phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine residues to decrease cell motility. These results provide new insight into PDPN phosphorylation dynamics and the role of PDPN in cell motility. Understanding novel mechanisms of PDPN intracellular signaling could assist with designing novel targeted chemotherapeutic agents and procedures.
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serines in the intracellular tail of podoplanin PDPN regulate cell motility
Journal of Biological Chemistry, 2013Co-Authors: Harini Krishnan, Maria I Ramirez, Todd W Miller, Evan Nevel, Yongquan Shen, Jhon A Ochoaalvarez, Meenakshi Lakshminarayanan, Mary C Williams, Gary S GoldbergAbstract:Abstract Podoplanin (PDPN) is a transmembrane receptor that affects the activities of Rho, ezrin, and other proteins to promote tumor cell motility, invasion, and metastasis. PDPN is found in many types of cancer and may serve as a tumor biomarker and chemotherapeutic target. The intracellular region of PDPN contains only two serines, and these are conserved in mammals including mice and humans. We generated cells from the embryos of homozygous null PDPN knock-out mice to investigate the relevance of these serines to cell growth and migration on a clear (PDPN-free) background. We report here that one or both of these serines can be phosphorylated by PKA (protein kinase A). We also report that conversion of these serines to nonphosphorylatable alanine residues enhances cell migration, whereas their conversion to phosphomimetic aspartate residues decreases cell migration. These results indicate that PKA can phosphorylate PDPN to decrease cell migration. In addition, we report that PDPN expression in fibroblasts causes them to facilitate the motility and viability of neighboring melanoma cells in coculture. These findings shed new light on how PDPN promotes cell motility, its role in tumorigenesis, and its utility as a functionally relevant biomarker and chemotherapeutic target.
Barbara Czarnocka - One of the best experts on this subject based on the ideXlab platform.
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podoplanin PDPN affects the invasiveness of thyroid carcinoma cells by inducing ezrin radixin and moesin e r m phosphorylation in association with matrix metalloproteinases
BMC Cancer, 2019Co-Authors: Justyna Sikorska, Damian Gawel, Hanna Domek, Magdalena Rudzinska, Barbara CzarnockaAbstract:Background Podoplanin (PDPN) is a mucin-type transmembrane glycoprotein specific to the lymphatic system. PDPN expression has been found in various human tumors and is considered to be a marker of cancer. We had previously shown that PDPN expression contributes to carcinogenesis in the TPC1 papillary thyroid cancer-derived cell line by enhancing cell migration and invasiveness. The aim of this study was to determine the effect of PDPN down-regulation in another thyroid cancer-derived cell line: BcPAP.
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The role of podoplanin in the biology of differentiated thyroid cancers.
PLOS ONE, 2014Co-Authors: Magdalena Rudzińska, Damian Gawel, Justyna Sikorska, Kamila Karpinska, Mirosław Kiedrowski, Tomasz Stępień, Magdalena Marchlewska, Barbara CzarnockaAbstract:Podoplanin (PDPN), a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell's malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis), a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC) tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression.
