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: Panida Lungchukiet, Yuefeng Sun, Ravi Kasiappan, Waise Quarni, Santo V Nicosia, Xiaohong Zhang, Wenlong Bai
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 148 Pg. 138-47 (Apr 2015) ISSN: 1879-1220 [Electronic] England
• PMID: 25448740 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Calcitriol
• Vitamins
• Calcitriol

Topics

• Animals
• Calcitriol (pharmacology)
• Carcinoma, Ovarian Epithelial
• Female
• Humans
• Mice
• Neoplasm Invasiveness
• Neoplasms, Glandular and Epithelial (drug therapy, metabolism, pathology)
• Omentum (drug effects, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Receptors, Calcitriol (metabolism)
• Vitamins (pharmacology)