Prostate specific membrane antigen produces pro-angiogenic laminin peptides downstream of matrix metalloprotease-2
Prostate specific membrane antigen produces pro-angiogenic laminin peptides downstream of matrix metalloprotease-2
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DOI：
10.1007/s10456-013-9360-y
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发表时间：
2013-10-01
期刊：
影响因子：
9.8
通讯作者：
Shapiro, Linda H.
中科院分区：
文献类型：
--
作者：
Conway, Rebecca E.;Joiner, Kyle;Shapiro, Linda H.
Prostate specific membrane antigen (PSMA) is a pro-angiogenic cell-surface protease that we previously demonstrated regulates blood vessel formation in a laminin and integrin beta(1)-dependent manner. Here, we examine the principal mechanism of PSMA activation of integrin beta(1). We show that digesting laminin sequentially with recombinant matrix metalloprotease-2 (MMP-2) and PSMA generates small peptides that enhance endothelial cell adhesion and migration in vitro. We also provide evidence that these laminin peptides activate adhesion via integrin alpha(6)beta(1) and focal adhesion kinase. Using an in vivo Matrigel implant assay, we show that these MMP/PSMA-derived laminin peptides also increase angiogenesis in vivo. Together, our results reveal a novel mechanism of PSMA activation of angiogenesis by processing laminin downstream of MMP-2.
