PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis

Abstract

Caveolae are specialized plasma membrane subdomains implicated in cellular functions such as migration, signalling and trafficking. Caveolin-1 and polymerase I and transcript release factor (PTRF)/cavin-1 are essential for caveola formation. Caveolin-1 is overexpressed and secreted in prostate tumors and promotes aggressiveness and angiogenesis. In contrast, a lack of PTRF expression is reported in prostate cancer, and ectopic PTRF expression in prostate cancer cells inhibits tumor growth and metastasis. We experimentally manipulated PTRF expression in three prostate cancer cell lines, namely the caveolin-1 positive cells PC3 and DU145 and the caveolin-1-negative LNCaP cells, to evaluate angiogenesis- and lymphangiogenesis-regulating functions of PTRF. We show that the conditioned medium of PTRF-expressing prostate cancer cells decreases ECs proliferation, migration and differentiation in vitro and ex vivo. This can occur independently from caveolin-1 expression and secretion or caveola formation, since the anti-angiogenic effects of PTRF were detected in caveolin-1-negative LNCaP cells. Additionally, PTRF expression in PC3 cells significantly decreased blood and lymphatic vessel densities in orthotopic tumors in mice. Our results suggest that the absence of PTRF in prostate cancer cells contributes significantly to tumour progression and metastasis by promoting the angiogenesis and lymphangiogenesis potential of the cancer cells, and this could be exploited for therapy.