Priming Endothelial Cells With a Melanoma-Derived Extracellular Matrix Triggers the Activation of αvβ3/VEGFR2 Axis
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...
Saved in:
Published in | Journal of cellular physiology Vol. 231; no. 11; pp. 2464 - 2473 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Blackwell Publishing Ltd
01.11.2016
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | Fundação e Coordenação de Apoio de Pessoal de Nível Superior - No. CAPES, #23038.007778/2014-21; No. N° AUXPE:0163/2015 ark:/67375/WNG-DJ1ZM0Q3-8 istex:028029383C51B20239DDE8F3DADA3F809EA16C71 ArticleID:JCP25358 Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil - No. CNPQ 301797/2013-7 Fundação de Amparo à Pesquisa do Rio de Janeiro - No. FAPERJ E-26/201.441/2014 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9541 1097-4652 |
DOI: | 10.1002/jcp.25358 |