Enzymatic Activity of Free-Prostate-SpecificAntigen (f-PSA) Is Not Required for Some of its Physiological Activities

Chadha, KC; Nair, BB; Chakravarthi, S; Zhou R.; Godoy A.; Mohler, JL; Aalinkeel, R; Schwartz, SA; Smith, GJ

Keywords: angiogenesis, prostate cancer, wound healing assay, human umbilical vein endothelial cells, antiangiogenic activity, in vitro angiogenesis assay, matrigel invasion assay

Abstract

BACKGROUND. Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS. Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc(2+). Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS. Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn(2+) had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-gamma; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION. Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity. Prostate 71:1680-1690, 2011. (C) 2011 Wiley-Liss, Inc.

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Título según WOS: Enzymatic Activity of Free-Prostate-SpecificAntigen (f-PSA) Is Not Required for Some of its Physiological Activities
Título de la Revista: Prostate
Volumen: 71
Número: 15
Editorial: Wiley
Fecha de publicación: 2011
Página de inicio: 1680
Página final: 1690
Idioma: English
DOI:

10.1002/pros.21385

Notas: ISI