Functional Angiogenic Mediators in Prostate Cancer
Abstract
The purpose of this study was to: (1) identify the key functional angiogenic mediators in the normal and diseased prostate, (2) determine the relationship between disease progression and angiogenic mediators in prostatic fluid; and, (3) determine the efficacy of the natural inhibitor thrombospondin-1 (TSP-1) in treating prostate cancer in model systems. Prostate cells secrete many molecules capable of regulating angiogenesis; however, which are functionally active in angiogenic regulation is unclear. We used an in vitro angiogenesis assay to identify the functional angiogenic mediators secreted by prostate cells, and quantified these factors in vitro by immunoblot or ELISA and in vivo by immunostaining human tissues. Normal prostate epithelial cell secretions were anti-angiogenic due to inhibitory 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 vascular endothelial growth factor (VEGF) whose secretion was increased. Immunolocalization confirmed that these changes also occurred in vivo. Thus, we identified the major functional angiogenic mediators in the prostate and have provided a detailed description of how normal angio-quiescent prostate tissue becomes angiogenic in disease states through both the down-regulation of the inhibitor TSP-1 and the up-regulation of the stimulatory FGF-2 and VEGF.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADB282212
Entities
People
- Jennifer A. Doll
Organizations
- Northwestern University