title: Suppression of epithelial ovarian cancer invasion into the omentum by 1α,25-dihydroxyvitamin D3 and its receptor.
abstract: Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer death in women, mainly because it has spread to intraperitoneal tissues such as the omentum in the peritoneal cavity by the time of diagnosis. In the present study, we established in vitro assays, ex vivo omental organ culture system and syngeneic animal tumor models using wild type (WT) and vitamin D receptor (VDR) null mice to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25D3) and VDR on EOC invasion. Treatment of human EOC cells with 1,25D3 suppressed their migration and invasion in monolayer scratch and transwell assays and ability to colonize the omentum in the ex vivo system, supporting a role for epithelial VDR in interfering with EOC invasion. Furthermore, VDR knockdown in OVCAR3 cells increased their ability to colonize the omentum in the ex vivo system in the absence of 1,25D3, showing a potential ligand-independent suppression of EOC invasion by epithelial VDR. In syngeneic models, ID8 tumors exhibited an increased ability to colonize omenta of VDR null over that of WT mice; pre-treatment of WT, not VDR null, mice with EB1089 reduced ID8 colonization, revealing a role for stromal VDR in suppressing EOC invasion. These studies are the first to demonstrate a role for epithelial and stromal VDR in mediating the activity of 1,25D3 as well as a 1,25D3-independent action of the VDR in suppressing EOC invasion. The data suggest that VDR-based drug discovery may lead to the development of new intervention strategies to improve the survival of patients with EOC at advanced stages. This article is part of a Special Issue entitled "Vitamin D Workshop".
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Panida
authors.initials: P
authors.lastname: Lungchukiet
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kasiappan
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Waise
authors.initials: W
authors.lastname: Quarni
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; Oncological Sciences, H. Lee Moffitt Cancer Center, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; Chemical Biology and Molecular Medicine, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; Oncological Sciences, H. Lee Moffitt Cancer Center, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; University of South Florida College of Medicine, and Programs of Cancer Biology & Evolution, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Departments of Pathology and Cell Biology, University of South Florida, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; Oncological Sciences, H. Lee Moffitt Cancer Center, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA; University of South Florida College of Medicine, and Programs of Cancer Biology & Evolution, H. Lee Moffitt Cancer Center, 12901 Bruce B. Downs Blvd., MDC 64, Tampa, FL 33612-4799, USA. Electronic address: wbai@health.usf.edu.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Bai
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009852:Omentum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D018167:Receptors, Calcitriol; D014815:Vitamins; D002117:Calcitriol
keywords: 1,25-Dihydroxyvitamin D(3); Omentum; Ovarian cancer; Tumor invasion; Vitamin D receptor