Abstract
Matrix metalloproteinases (MMPs) have a critical role in vascular remodeling, tumor progression and angiogenesis. VEGFR2, the main receptor for VEGF, expressed on endothelial cells has a role in promoting cell survival, proliferation and angiogenesis. Since MMP‐1 expression is positively correlated with a variety of cancers, we tested the hypothesis that MMP‐1 has a direct effect on endothelial cells, specifically by increasing their levels of VEGFR2. Endothelial cells were treated with active MMP‐1 and analyzed for VEGFR2 mRNA, protein levels and specific signaling pathways governed by the receptor. We found that treatment with MMP‐1 significantly augmented mRNA levels and protein expression of VEGFR2 in endothelial cells. Furthermore, VEGF‐A dependent phosphorylation of intracellular signaling molecules such as ERK and Akt were higher in MMP‐1 treated cells. We conclude that MMP‐1 promotes VEGFR2 expression on endothelial cells and provides, at least in part, a mechanism by which MMPs in a tumor microenvironment can promote cell proliferation and angiogenesis.Research supported by NIH grant HL 10881
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