Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo

Fortier, Anne H.; Holaday, John W.; Liang, Hong; Dey, Chinmoy Sankar; Grella, Davida K.; Holland-Linn, Janel; Vu, Hong; Plum, Stacy M.; Nelson, Barbara J.

doi:10.1002/pros.10256

Cited by 65 publications

(50 citation statements)

References 21 publications

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“…Although PSA is widely used as a serum marker to screen for PC, a pathophysiological role is uncertain (27). Novel biological properties of PSA including its antiangiogenic activity have been reported (28). These observations implicate the presence of receptors or substrates for PSA on the surface of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Romanov¹,

Whyard²,

Adler³

et al. 2004

Cancer Research

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Bone metastasis is the most frequent complication of prostate cancer (PC). Elucidation of the biological basis of this specificity is required for the development of approaches for metastatic inhibition. We investigated the possibility that the preferential attachment of PC cells to bone marrow endothelium (as opposed to endothelium from other organs) affects this specificity. We selected, from peptide phage-displayed libraries, peptide ligands to surfaces of PC cells (C4-2B) attenuated (30 -40%) binding of C4-2B cells to bone marrow endothelial cells (BMECs). We then determined the molecules on the surface of C4-2B cells interacted with the selected peptides using column affinity chromatography and a cDNA expression phage-displayed library generated from C4-2B cells in T7 phage. We identified a phage from the cDNA library that specifically bound to one of the selected peptides-L11. This phage displayed the amino acid sequence homologous for the COOH-terminal portion of prostatespecific antigen (PSA). To examine the possible direct involvement of PSA in the interactions between PC and BMECs, we performed a cell-cell adhesion assay. Antibodies to PSA attenuated PC cells adhesion to BMECs. In addition, exogenous proteolytically active PSA modulated this adhesion. Finally, inactivation of mRNA coding PSA by a small interfering RNA (siRNA) diminished C4-2B cell adhesion to BMECs. These results indicate that PSA expressed as secreted and surface-associated molecules in C4-2B cells is involved in cell-cell interactions and/or digests components of bone marrow endothelium for preferential adhesion and penetration of PC cells. The suggested experimental approach is a promising strategy for identification of cell surface molecules involved in intercellular interactions.

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Section: Discussionmentioning

confidence: 99%

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Romanov¹,

Whyard²,

Adler³

et al. 2004

Cancer Research

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“…On the other hand, PSA/KLK3 (Heidtmann et al , 1999 ), KLK5 (Michael et al , 2005 ), KLK6 (Bayes et al , 2004 ), and KLK13 proteolytic activity upon plasminogen releases angiostatin-like fragments in vitro , which block endothelial cells ' proliferation and angiogenesis. Moreover, PSA/KLK3 treatment of endothelial cells reduces their proliferation and migration capacities, which is mainly attributed to a PSA/KLK3-mediated inhibition of the treated cells ' responses to fi broblast growth factor (FGF) and vascular endothelial growth factor (VEGF) (Fortier et al , 1999 ), whereas the angiogenesis-inhibition potential was also demon strated in vivo (Fortier et al , 2003 ). The antiangiogenic role of PSA/KLK3 is also supported by the increased angiogenesis observed in prostate cancer specimens with decreased PSA/KLK3 expression (Papadopoulos et al , 2001 ).…”

Section: Kallikrein-related Peptidases and Tumor Progressionmentioning

confidence: 99%

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

Avgeris

Mavridis

Scorilas

2012

Biological Chemistry

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Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2 -15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identifi cation as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide signifi cant benefi ts for the management of cancer patients.

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“…The primary regulator of PSA expression in the human prostate is AR and its gene is located on chromosome Xq-11-12 [32]. AR results in the induction of PSA expression through three androgen response elements (AREs) located in the proximal 6 kb of the PSA promoter [33].…”

Section: Crosstalk Between Psa and Armentioning

confidence: 99%

Role of Prostate Specific Antigen (PSA) in Pathogenesis of Prostate Cancer

Altuwaijri¹

2012

JCT

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Prostate cancer (PCa) is most common diagnosed cancer in men and it is second most common cause of male cancer death. Many factors have been implicated in the pathogenesis of PCa. Although many papers have discussed the prostate specific antigen (PSA) as biomarker of PCa, very few have addressed its rule in the carcinogenesis, metastasis and invasion of PCa. In this article we will review the pathological role of PSA, as a potential target in the therapeutics of PCa.

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Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo

Abstract: 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.

Cited by 65 publications

References 21 publications

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

Role of Prostate Specific Antigen (PSA) in Pathogenesis of Prostate Cancer

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