Abstract 456: 25-Hydroxyvitamin D3 inhibits clonogenic growth and regulates expression of multiple cytokines/chemokines in co-culture of colon cancer and macrophage-like THP-1 cells

Abstract

Abstract Colon cancer cells interact with immune cells in vivo, creating a microenvironment which affects both tumor growth and treatment. Macrophages are often the most abundant immune cells in the tumor microenvironment and are involved in inflammation. Since inflammation is tightly associated with colon carcinogenesis, it is important to understand how vitamin D affects the interaction between colon epithelial cells and macrophages. In this study, we used a co-culture system to examine the role of 25-hydroxyvitamin D3 (25(OH)D3) on the clonogenic growth of colon cancer cells and on the profiling of cytokines/chemokines. 25(OH)D3 at 250 nM had minor effect on clonogenic growth in CaCo-2 cells, co-culture of macrophage-like THP-1 cells with CaCo-2 cells significantly stimulated the clonogenic growth of CaCo-2 cells in the absence of 25(OH)D3. However, in the presence of 25(OH)D3, THP-1 cells failed to stimulate the the clonogenic growth of CaCo-2 cells. Cytokine antibody array demonstrated that several cytokines were differentially expressed in the medium after co-culture of the two cell lines for 2 days in the absence of 25(OH)D3. These include increased expression of GROα, MCP-1 and decreased expression of TNFα, Angiogenin; however, in the presence of 25(OH)D3, MCP-2 and MDC were significantly induced and TNFα level was restored. Proliferation assay showed that MCP-2 and MDC had minor or no effect on cell proliferation in CaCo-2 cells, suggesting that these chemokines mainly target macrophages. 25(OH)D3 treatment of THP-1 cells for 24h also induced CYP24, an immediate vitamin D target gene and enhanced MDC and MCP-2 expression as evaluated by qRT-PCR. These results demonstrate that 25(OH)D3 at 250 nM might selectively target macrophages in a co-culture system with colon cells and block the interaction between colon cancer cells and macrophages, which may result in prevention of inflammation. [Supported by NCI R01 CA121157]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 456. doi:10.1158/1538-7445.AM2011-456