Priming Endothelial Cells With a Melanoma-Derived Extracellular Matrix Triggers the Activation of αvß3/VEGFR2 Axis.
J Cell Physiol
; 231(11): 2464-73, 2016 11.
Article
in En
| MEDLINE
| ID: mdl-27420801
ABSTRACT
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 αvß3 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Vascular Endothelial Growth Factor Receptor-2
/
Integrin alphaVbeta3
/
Endothelial Cells
/
Extracellular Matrix
/
Melanoma
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Cell Physiol
Year:
2016
Document type:
Article
Affiliation country:
Brazil