title: Inhibition of stromal PlGF suppresses the growth of prostate cancer xenografts.
abstract: The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.
authors.affiliation: Laboratory for Molecular Cellular Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria. karin.zins@meduniwien.ac.at
authors.forename: Karin
authors.initials: K
authors.lastname: Zins
authors.forename: Anita
authors.initials: A
authors.lastname: Thomas
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
authors.forename: Dietmar
authors.initials: D
authors.lastname: Abraham
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D051379:Mice; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; D000072483:Placenta Growth Factor