Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo
- 20 May 2003
- journal article
- Published by Wiley in The Prostate
- Vol. 56 (3) , 212-219
- https://doi.org/10.1002/pros.10256
Abstract
BACKGROUND: Prostate specific antigen (PSA) is a kallikrein family member with serine protease activity commonly used as a diagnostic marker for prostate cancer. We recently described anti‐angiogenic properties of PSA [Fortier et al.: JNCI 91:1635–1640].METHODS: Two forms of PSA were cloned and expressed in Pichia pastoris: one, an intact PSA with an N‐terminus of IVGGVS…; the second, an N‐1 PSA variant. The recombinant proteins were tested for serine protease activity and for anti‐angiogenic activity in vitro and in vivo.RESULTS: The rate of substrate hydrolysis by the intact recombinant PSA was similar to that of PSA isolated and purified from human seminal plasma. In contrast, the N‐1 PSA variant lacked serine protease activity. In an endothelial cell migration assay, the concentration that resulted in 50% inhibition (IC50) was: 0.5 μM for native PSA, 0.5 μM for intact recombinant protein, and 0.1 μM for the N‐1 variant PSA. Both the intact recombinant and the N‐1 recombinant PSA inhibited angiogenesis in vivo.CONCLUSIONS: Purified recombinant PSA inhibits angiogenesis, proving the concept that PSA is an anti‐angiogenic, and serine protease activity, as determined by synthetic substrate hydrolysis, is distinct from the anti‐angiogenic properties of PSA. Prostate 56: 212–219, 2003.Keywords
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