PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells

In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known abou...
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Autor*in:	Ernst J.A. Steller [verfasserIn] Danielle A. Raats [verfasserIn] Jan Koster [verfasserIn] Bert Rutten [verfasserIn] Klaas M. Govaert [verfasserIn] Benjamin L. Emmink [verfasserIn] Nikol Snoeren [verfasserIn] Sander R. van Hooff [verfasserIn] Frank C.P. Holstege [verfasserIn] Coen Maas [verfasserIn] Rinkes Inne H.M. Borel [verfasserIn] Onno Kranenburg [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Übergeordnetes Werk:	In: Neoplasia: An International Journal for Oncology Research - Elsevier, 2008, 15(2013), 2, Seite 204-217
Übergeordnetes Werk:	volume:15 ; year:2013 ; number:2 ; pages:204-217

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1593/neo.121726

Katalog-ID:	DOAJ034388893

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520			\|a In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.
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700	0		\|a Klaas M. Govaert \|e verfasserin \|4 aut
700	0		\|a Benjamin L. Emmink \|e verfasserin \|4 aut
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700	0		\|a Sander R. van Hooff \|e verfasserin \|4 aut
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700	0		\|a Rinkes Inne H.M. Borel \|e verfasserin \|4 aut
700	0		\|a Onno Kranenburg \|e verfasserin \|4 aut
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allfields	10.1593/neo.121726 doi (DE-627)DOAJ034388893 (DE-599)DOAJ91547ac17fc44106b0019f7cb7942410 DE-627 ger DE-627 rakwb eng RC254-282 Ernst J.A. Steller verfasserin aut PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Danielle A. Raats verfasserin aut Jan Koster verfasserin aut Bert Rutten verfasserin aut Klaas M. Govaert verfasserin aut Benjamin L. Emmink verfasserin aut Nikol Snoeren verfasserin aut Sander R. van Hooff verfasserin aut Frank C.P. Holstege verfasserin aut Coen Maas verfasserin aut Rinkes Inne H.M. Borel verfasserin aut Onno Kranenburg verfasserin aut In Neoplasia: An International Journal for Oncology Research Elsevier, 2008 15(2013), 2, Seite 204-217 (DE-627)320468690 (DE-600)2008231-9 14765586 nnns volume:15 year:2013 number:2 pages:204-217 https://doi.org/10.1593/neo.121726 kostenfrei https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 kostenfrei http://www.sciencedirect.com/science/article/pii/S1476558613800309 kostenfrei https://doaj.org/toc/1476-5586 Journal toc kostenfrei https://doaj.org/toc/1522-8002 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 15 2013 2 204-217
spelling	10.1593/neo.121726 doi (DE-627)DOAJ034388893 (DE-599)DOAJ91547ac17fc44106b0019f7cb7942410 DE-627 ger DE-627 rakwb eng RC254-282 Ernst J.A. Steller verfasserin aut PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Danielle A. Raats verfasserin aut Jan Koster verfasserin aut Bert Rutten verfasserin aut Klaas M. Govaert verfasserin aut Benjamin L. Emmink verfasserin aut Nikol Snoeren verfasserin aut Sander R. van Hooff verfasserin aut Frank C.P. Holstege verfasserin aut Coen Maas verfasserin aut Rinkes Inne H.M. Borel verfasserin aut Onno Kranenburg verfasserin aut In Neoplasia: An International Journal for Oncology Research Elsevier, 2008 15(2013), 2, Seite 204-217 (DE-627)320468690 (DE-600)2008231-9 14765586 nnns volume:15 year:2013 number:2 pages:204-217 https://doi.org/10.1593/neo.121726 kostenfrei https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 kostenfrei http://www.sciencedirect.com/science/article/pii/S1476558613800309 kostenfrei https://doaj.org/toc/1476-5586 Journal toc kostenfrei https://doaj.org/toc/1522-8002 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 15 2013 2 204-217
allfields_unstemmed	10.1593/neo.121726 doi (DE-627)DOAJ034388893 (DE-599)DOAJ91547ac17fc44106b0019f7cb7942410 DE-627 ger DE-627 rakwb eng RC254-282 Ernst J.A. Steller verfasserin aut PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Danielle A. Raats verfasserin aut Jan Koster verfasserin aut Bert Rutten verfasserin aut Klaas M. Govaert verfasserin aut Benjamin L. Emmink verfasserin aut Nikol Snoeren verfasserin aut Sander R. van Hooff verfasserin aut Frank C.P. Holstege verfasserin aut Coen Maas verfasserin aut Rinkes Inne H.M. Borel verfasserin aut Onno Kranenburg verfasserin aut In Neoplasia: An International Journal for Oncology Research Elsevier, 2008 15(2013), 2, Seite 204-217 (DE-627)320468690 (DE-600)2008231-9 14765586 nnns volume:15 year:2013 number:2 pages:204-217 https://doi.org/10.1593/neo.121726 kostenfrei https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 kostenfrei http://www.sciencedirect.com/science/article/pii/S1476558613800309 kostenfrei https://doaj.org/toc/1476-5586 Journal toc kostenfrei https://doaj.org/toc/1522-8002 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 15 2013 2 204-217
allfieldsGer	10.1593/neo.121726 doi (DE-627)DOAJ034388893 (DE-599)DOAJ91547ac17fc44106b0019f7cb7942410 DE-627 ger DE-627 rakwb eng RC254-282 Ernst J.A. Steller verfasserin aut PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Danielle A. Raats verfasserin aut Jan Koster verfasserin aut Bert Rutten verfasserin aut Klaas M. Govaert verfasserin aut Benjamin L. Emmink verfasserin aut Nikol Snoeren verfasserin aut Sander R. van Hooff verfasserin aut Frank C.P. Holstege verfasserin aut Coen Maas verfasserin aut Rinkes Inne H.M. Borel verfasserin aut Onno Kranenburg verfasserin aut In Neoplasia: An International Journal for Oncology Research Elsevier, 2008 15(2013), 2, Seite 204-217 (DE-627)320468690 (DE-600)2008231-9 14765586 nnns volume:15 year:2013 number:2 pages:204-217 https://doi.org/10.1593/neo.121726 kostenfrei https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 kostenfrei http://www.sciencedirect.com/science/article/pii/S1476558613800309 kostenfrei https://doaj.org/toc/1476-5586 Journal toc kostenfrei https://doaj.org/toc/1522-8002 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 15 2013 2 204-217
allfieldsSound	10.1593/neo.121726 doi (DE-627)DOAJ034388893 (DE-599)DOAJ91547ac17fc44106b0019f7cb7942410 DE-627 ger DE-627 rakwb eng RC254-282 Ernst J.A. Steller verfasserin aut PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Danielle A. Raats verfasserin aut Jan Koster verfasserin aut Bert Rutten verfasserin aut Klaas M. Govaert verfasserin aut Benjamin L. Emmink verfasserin aut Nikol Snoeren verfasserin aut Sander R. van Hooff verfasserin aut Frank C.P. Holstege verfasserin aut Coen Maas verfasserin aut Rinkes Inne H.M. Borel verfasserin aut Onno Kranenburg verfasserin aut In Neoplasia: An International Journal for Oncology Research Elsevier, 2008 15(2013), 2, Seite 204-217 (DE-627)320468690 (DE-600)2008231-9 14765586 nnns volume:15 year:2013 number:2 pages:204-217 https://doi.org/10.1593/neo.121726 kostenfrei https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 kostenfrei http://www.sciencedirect.com/science/article/pii/S1476558613800309 kostenfrei https://doaj.org/toc/1476-5586 Journal toc kostenfrei https://doaj.org/toc/1522-8002 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 15 2013 2 204-217
language	English
source	In Neoplasia: An International Journal for Oncology Research 15(2013), 2, Seite 204-217 volume:15 year:2013 number:2 pages:204-217
sourceStr	In Neoplasia: An International Journal for Oncology Research 15(2013), 2, Seite 204-217 volume:15 year:2013 number:2 pages:204-217
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Neoplasia: An International Journal for Oncology Research
authorswithroles_txt_mv	Ernst J.A. Steller @@aut@@ Danielle A. Raats @@aut@@ Jan Koster @@aut@@ Bert Rutten @@aut@@ Klaas M. Govaert @@aut@@ Benjamin L. Emmink @@aut@@ Nikol Snoeren @@aut@@ Sander R. van Hooff @@aut@@ Frank C.P. Holstege @@aut@@ Coen Maas @@aut@@ Rinkes Inne H.M. Borel @@aut@@ Onno Kranenburg @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
hierarchy_top_id	320468690
id	DOAJ034388893
language_de	englisch
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callnumber-first	R - Medicine
author	Ernst J.A. Steller
spellingShingle	Ernst J.A. Steller misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
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topic_title	RC254-282 PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
topic	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
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title_full	PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
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author_browse	Ernst J.A. Steller Danielle A. Raats Jan Koster Bert Rutten Klaas M. Govaert Benjamin L. Emmink Nikol Snoeren Sander R. van Hooff Frank C.P. Holstege Coen Maas Rinkes Inne H.M. Borel Onno Kranenburg
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title_sort	pdgfrb promotes liver metastasis formation of mesenchymal-like colorectal tumor cells
callnumber	RC254-282
title_auth	PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
abstract	In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.
abstractGer	In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.
abstract_unstemmed	In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.
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title_short	PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
url	https://doi.org/10.1593/neo.121726 https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 http://www.sciencedirect.com/science/article/pii/S1476558613800309 https://doaj.org/toc/1476-5586 https://doaj.org/toc/1522-8002
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author2	Danielle A. Raats Jan Koster Bert Rutten Klaas M. Govaert Benjamin L. Emmink Nikol Snoeren Sander R. van Hooff Frank C.P. Holstege Coen Maas Rinkes Inne H.M. Borel Onno Kranenburg
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up_date	2024-07-03T22:57:03.009Z
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Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Danielle A. 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PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells

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