Angiogenesis

, Volume 16, Issue 4, pp 847–860

Prostate specific membrane antigen produces pro-angiogenic laminin peptides downstream of matrix metalloprotease-2

  • Rebecca E. Conway
  • Kyle Joiner
  • Alex Patterson
  • David Bourgeois
  • Robert Rampp
  • Benjamin C. Hannah
  • Samantha McReynolds
  • John M. Elder
  • Hannah Gilfilen
  • Linda H. Shapiro
Original Paper

DOI: 10.1007/s10456-013-9360-y

Cite this article as:
Conway, R.E., Joiner, K., Patterson, A. et al. Angiogenesis (2013) 16: 847. doi:10.1007/s10456-013-9360-y

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.

Keywords

AngiogenesisExtracellular matrixProstate specific membrane antigenMatrix metalloproteases

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Rebecca E. Conway
    • 1
    • 2
  • Kyle Joiner
    • 1
  • Alex Patterson
    • 1
  • David Bourgeois
    • 1
  • Robert Rampp
    • 1
  • Benjamin C. Hannah
    • 1
  • Samantha McReynolds
    • 1
  • John M. Elder
    • 1
  • Hannah Gilfilen
    • 1
  • Linda H. Shapiro
    • 2
  1. 1.Department of Biology, College of Arts and SciencesLipscomb UniversityNashvilleUSA
  2. 2.Department of Cell Biology, Center for Vascular BiologyUniversity of Connecticut Health CenterFarmingtonUSA