Prostate specific membrane antigen produces pro-angiogenic laminin peptides downstream of matrix metalloprotease-2
RE Conway, K Joiner, A Patterson, D Bourgeois… - Angiogenesis, 2013 - Springer
RE Conway, K Joiner, A Patterson, D Bourgeois, R Rampp, BC Hannah, S McReynolds…
Angiogenesis, 2013•SpringerProstate specific membrane antigen (PSMA) is a pro-angiogenic cell-surface protease that
we previously demonstrated regulates blood vessel formation in a laminin and integrin β 1-
dependent manner. Here, we examine the principal mechanism of PSMA activation of
integrin β 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 …
we previously demonstrated regulates blood vessel formation in a laminin and integrin β 1-
dependent manner. Here, we examine the principal mechanism of PSMA activation of
integrin β 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 …
Abstract
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 β1-dependent manner. Here, we examine the principal mechanism of PSMA activation of integrin β1. 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 α6β1 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.
Springer