title: 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.
authors.affiliation: The University of Queensland, School of Pharmacy, QLD, Australia.
authors.forename: Zeyad D
authors.initials: ZD
authors.lastname: Nassar
authors.forename: Hyeongsun
authors.initials: H
authors.lastname: Moon
authors.forename: Tam
authors.initials: T
authors.lastname: Duong
authors.forename: LiQi
authors.initials: L
authors.lastname: Neo
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Hill
authors.forename: Mathias
authors.initials: M
authors.lastname: Francois
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Parat
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D042583:Lymphangiogenesis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C497835:CAVIN1 protein, human; D051242:Caveolin 1; D016601:RNA-Binding Proteins