title: WNT5A has anti-prostate cancer effects in vitro and reduces tumor growth in the skeleton in vivo.
abstract: Prostate cancer is the most frequent malignancy in men, and a major cause of prostate cancer-related death is attributable to bone metastases. WNT5A is known to influence the clinical outcome of various cancer types, including prostate cancer, but the exact mechanisms remain unknown. The goal of this study was to assess the relevance of WNT5A for the development and progression of prostate cancer. WNT5A expression was determined in a cDNA and tissue microarray of primary tumor samples in well-defined cohorts of patients with prostate cancer. Compared with benign prostate tissue, the expression of WNT5A and its receptor Frizzled-5 was higher in prostate cancer, and patients with a WNT5A expression above the median had a higher probability of survival after 10 years. Using different osteotropic human prostate cancer cell lines, the influence of WNT5A overexpression and knock-down on proliferation, migration, and apoptosis was assessed. In vitro, WNT5A overexpression induced prostate cancer cell apoptosis and reduced proliferation and migration, whereas WNT5A knock-down showed opposite effects. In vivo, different xenograft models were used to determine the effects of WNT5A on tumor growth. Local tumor growth and tumor growth in the bone microenvironment was considerably diminished after WNT5A overexpression in PC3 cells. WNT5A exhibits antitumor effects in prostate cancer cells and may be suitable as a prognostic marker and therapeutic target for prostate cancer and associated skeletal metastases.
authors.affiliation: Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thiele
authors.forename: Andy
authors.initials: A
authors.lastname: Göbel
authors.forename: Tilman D
authors.initials: TD
authors.lastname: Rachner
authors.forename: Susanne
authors.initials: S
authors.lastname: Fuessel
authors.forename: Michael
authors.initials: M
authors.lastname: Froehner
authors.forename: Michael H
authors.initials: MH
authors.lastname: Muders
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Baretton
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bernhardt
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
authors.forename: Claus C
authors.initials: CC
authors.lastname: Glüer
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
keywords: APOPTOSIS; BONE METASTASES; PROSTATE CANCER; TUMOR-INDUCED BONE DISEASE; WNT5A