Abstract 3747: The impact of lipid inflammatory mediators on colon cancer initiating cells.

Past studies links the lipid inflammatory mediators at the tumor microenvironment to the colorectal cancer, however their impact on the colon cancer initiating cells (CICs) is largely unknown. Accordingly, the present study aimed to identify the possible link between lipid inflammatory mediators and CICs. In lack of robust marker for identifying colon CICs, we initially screen five different colon cancer cell lines (HCT-116, Caco-2, SW-480 SW-620 and HT-29) for their percentage occurrence using well-established stem cell markers i.e. CD133, CD44 and ALDH. The Flow cytometeric sorting of CD133, CD44 and ALDH subpopulations showed large variation in their population size in these cell lines. Further we noted that ALDH is relatively better marker of these to identify CICs. This statement was based on our observation of markedly increased capacity of ALDH + cells to produce colonies rather than ALDH − cells. We sorted ALDH + /CICs and investigated the effect of lipid inflammatory mediators such as leukotriene D 4 (LTD 4 ) or prostaglandin E 2 (PGE 2 ) on these cells. It was noted that LTD 4 and PGE 2 stimulations not only enriched the relative population of ALDH + cells; it also greatly improved the colony forming capacity of these cells. Moreover, we observed that ALDH + cells were more resistant to 5-Fluorouracil (5-FU) treatment compared to ALDH − cells. Furthermore the qPCR data revealed that Bcl-2, COX-2, Bcl-3, ALDH1B1, GLI1 and KLF4 genes were largely amplified in ALDH + cells in presence of LTD 4 or PGE 2 , indicating their probable impact on the stemness pool of these cells. In conclusion our study shows that lipid inflammatory mediators can affect the survival and stemness of CICs. Citation Format: Anita Sjolander, Kishan Bellamkonda, Wondossen Sime. The impact of lipid inflammatory mediators on colon cancer initiating cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2013-3747