Abstract 411: 1,25(OH)2D3 deficiency accelerates colon cancer progression via microenvironmental regulation

Abstract

Abstract Epidemiologic studies have revealed that low serum vitamin D levels are associated with an increased risk of colon cancer and inflammatory diseases such as inflammatory bowel disease (IBD) while underlying biological mechanisms remain largely unknown. It is also well established that tumor microenvironment plays an essential role in tumor progression. In this study, we sought to determine whether 1,25(OH)2D3 deficiency has a direct impact on colon cancer by using 25-hydroxyvitamin D 1-hydroxylase knockout [1α(OH)ase−/−] mice that had been fed with a rescue diet (high calcium, phosphate and lactose) from weaning. We injected CT26.WT cells (a murine colon cancer cell line) into 1α(OH)ase−/- and wild-type (WT) mice repectively and found that 1,25(OH)2D3 deficiency accelerated the growth of xenografted colon tumors. In the AOM/DSS model, heterozygous 1α(OH)ase+/− mice increased the multiplicity and size of colon tumors. Compared to WT mice, 1α(OH)ase−/− mice exhibited an increase of DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines in their colon stromal cells. These results suggest that 1,25(OH)2D3 deficiency may have a direct effect on colon cancer development, at least in part, by influencing tumor microenvironment. Note: This abstract was not presented at the meeting. Citation Format: Xiaoqin Yuan, Yun Liu, Lulu Chen, Dengshun Miao. 1,25(OH)2D3 deficiency accelerates colon cancer progression via microenvironmental regulation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 411. doi:10.1158/1538-7445.AM2015-411