Priming Endothelial Cells With a Melanoma-Derived Extracellular Matrix Triggers the Activation of αvβ3/VEGFR2 Axis
| Autor: | Renata Machado Brandão-Costa, Victor Midlej, Edward Helal-Neto, Roberta Saldanha-Gama, Verônica Morandi, Cristiane Ribeiro-Pereira, Christina Barja-Fidalgo, Marlene Benchimol |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tumor microenvironment Physiology Angiogenesis Cellular differentiation Clinical Biochemistry Integrin Cell Biology Biology Cell biology Endothelial stem cell Fibronectin Extracellular matrix 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis biology.protein Cell adhesion |
| Zdroj: | Journal of Cellular Physiology. 231:2464-2473 |
| ISSN: | 0021-9541 |
| DOI: | 10.1002/jcp.25358 |
| Popis: | The unique composition of tumor-produced extracellular matrix (ECM) can be a determining factor in changing the profile of endothelial cells in the tumor microenvironment. As the main receptor for ECM proteins, integrins can activate a series of signaling pathways related to cell adhesion, migration, and differentiation of endothelial cells that interact with ECM proteins. We studied the direct impact of the decellularized ECM produced by a highly metastatic human melanoma cell line (MV3) on the activation of endothelial cells and identified the intracellular signaling pathways associated with cell differentiation. Our data show that compared to the ECM derived from a human melanocyte cell line (NGM-ECM), ECM produced by a melanoma cell line (MV3-ECM) is considerably different in ultrastructural organization and composition and possesses a higher content of tenascin-C and laminin and a lower expression of fibronectin. When cultured directly on MV3-ECM, endothelial cells change morphology and show increased adhesion, migration, proliferation, and tubulogenesis. Interaction of endothelial cells with MV3-ECM induces the activation of integrin signaling, increasing FAK phosphorylation and its association with Src, which activates VEGFR2, potentiating the receptor response to VEGF. The blockage of αvβ3 integrin inhibited the FAK-Src association and VEGFR activation, thus reducing tubulogenesis. Together, our data suggest that the interaction of endothelial cells with the melanoma-ECM triggers integrin-dependent signaling, leading to Src pathway activation that may potentiate VEGFR2 activation and up-regulate angiogenesis. J. Cell. Physiol. 231: 2464-2473, 2016. © 2016 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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