دورية أكاديمية
PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells
| العنوان: | PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells |
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| المؤلفون: | 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 |
| المصدر: | Neoplasia: An International Journal for Oncology Research, Vol 15, Iss 2, Pp 204-217 (2013) |
| بيانات النشر: | Elsevier, 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1476-5586 1522-8002 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S1476558613800309; https://doaj.org/toc/1476-5586; https://doaj.org/toc/1522-8002 |
| DOI: | 10.1593/neo.121726 |
| URL الوصول: | https://doaj.org/article/91547ac17fc44106b0019f7cb7942410 |
| رقم الأكسشن: | edsdoj.91547ac17fc44106b0019f7cb7942410 |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 14765586 15228002 |
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| DOI: | 10.1593/neo.121726 |