Prostaglandin E2 Promotes Colorectal Cancer Stem-Like Cell Expansion And Metastasis

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAEmerging evidence suggests that chronic inflammation and inflammatory mediators contribute to cancer stem-like cell (CSLC) formation, maintenance, and expansion. However, the mechanisms underlying their contribution to CSLC regulation are poorly understood. Here we demonstrate that an inflammatory mediator, prostaglandin E2 (PGE2), induces colorectal CSLC expansion in vivo and in vitro. PGE2 also accelerates liver metastatic tumor incidence and numbers in an orthotopic model. Furthermore, we show that NF-κB is required for PGE2 induction of CSLCs and colorectal tumor metastatic spread. PI3K and MAPK pathways mediate PGE2 activation of NF-κB in induction of CSLCs. These results demonstrate that PGE2 induces colorectal CSLC expansion by activating NF-κB via PI3K-Akt and MAPK pathways. Our findings not only uncover a previously unrecognized role of PGE2 in induction of CSLCs and metastasis, but also may delineate a novel therapeutic approach for CRC patients by targeting CSLCs via inhibition of the PGE2 signaling pathway.Citation Format: Dingzhi Wang, Lingchen Fu, Haiyan Sun, Raymond N. DuBois. Prostaglandin E2 promotes colorectal cancer stem-like cell expansion and metastasis. [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 1523. doi:10.1158/1538-7445.AM2015-1523