Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate.
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.
Doll
J A
JA
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA. j-doll@northwestern.edu
Reiher
F K
FK
Crawford
S E
SE
Pins
M R
MR
Campbell
S C
SC
Bouck
N P
NP
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011467:Prostate / Q000098:blood supply* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2