Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate. Prostate 2001 Dec 01;49(4):293-305
Date
12/18/2001Pubmed ID
11746276DOI
10.1002/pros.10025Scopus ID
2-s2.0-0034747320 (requires institutional sign-in at Scopus site) 120 CitationsAbstract
BACKGROUND: Prostate cells secrete many molecules capable of regulating angiogenesis; however, which of these actually function as essential regulators of neovascularization is not yet clear.
METHODS: Functional angiogenic mediators secreted by normal and diseased prostate cells were identified using an in vitro angiogenesis assay. These factors were quantified by immunoblot or ELISA and localized in tissue by immunohistochemistry.
RESULTS: Normal prostate epithelial cell secretions were anti-angiogenic due to inhibitory thrombospondin-1 (TSP-1) whereas this inhibitor was decreased in the pro-angiogenic secretions derived from benign prostatic hyperplasia (BPH) and cancer cells. This pro-angiogenic activity depended primarily on fibroblast growth factor-2 (FGF-2) and/or vascular endothelial growth factor (VEGF) whose secretion was increased. Immunolocalization studies confirmed that the changes detected in vitro also occurred in vivo.
CONCLUSIONS: During disease progression in the prostate, production of TSP-1, the major inhibitor, is down-regulated while that of stimulatory FGF-2 and/or VEGF rise, leading to the induction of the new vessels necessary to support tumor growth.
Author List
Doll JA, Reiher FK, Crawford SE, Pins MR, Campbell SC, Bouck NPAuthor
Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Blotting, Western
Endothelial Growth Factors
Enzyme-Linked Immunosorbent Assay
Epithelial Cells
Fibroblast Growth Factor 2
Humans
Immunohistochemistry
Lymphokines
Male
Neovascularization, Pathologic
Neovascularization, Physiologic
Prostate
Prostatic Hyperplasia
Prostatic Neoplasms
Thrombospondin 1
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
