Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis

Up-regulation of caveolin-1 (cav-1) has been implicated in human prostate cancer progression/metastasis and shown to promote cancer cell survival. It has also been shown that cav-1 is secreted by tumor cells and may regulate the growth, functional activities, and migration of vascular endothelial cells. However, the relationship of cav-1 expression in prostate cancer cells and tumor associated endothelial cells (TAEC) to tumor-associated angiogenesis remains to be investigated. Dual immunofluorescent labeling with antibodies to CD34 and cav-1 was performed on 56 prostate cancer specimens obtained by radical prostatectomy and stratified according to cav-1 positivity in cancer cells. The tumor microvessel densities (MVD) and cav-1 expression in TAEC within these specimens were measured and correlated with cav-1 expression in prostate cancer cells. The MVD values were significantly higher in cav-1-positive (n = 25) than in the cav-1-negative (n = 31) tumors (median of 44 versus 25 vessels/field, P = .0140). Additional studies showed that the cav-1 positivity in microvessels within tumor specimens was significantly less frequent than in the blood vessels of benign prostatic tissues (94.4% versus 98.6%, P = .0012). In contrast, the percentage of cav-1-positive TAEC in cav-1-positive tumors was significantly higher than in cav-1-negative tumors (95.8% versus 92.7%, P = .0024). This increased cav-1 positivity in TAEC was predominantly confined to regions with cav-1-positive tumor cells corresponding to the higher percentage of cav-1-positive microvessels within these regions in cav-1-positive, as opposed to cav-1-negative tumors (P = .0086). These positive correlations provide new evidence for the involvement of prostate cancer cell derived cav-1 in mediating angiogenesis during prostate cancer progression. They also establish a conceptual framework for further investigation of cav-1 proangiogenic activities.