8th Annual BMRP Investigator Meeting - Abstract
Colitis Derived Tumorigenic Stem Cells and the Inflammatory Bowel
Emina H. Huang1,2,a, Joseph E. Carpentino1,2, Robert C. Fisher1,2, Tata R. Goluguri1 and Edward W. Scott2
1Departments of Surgery and 2Molecular Genetics and Microbiology, University of Florida (Gainesville, U.S.A.)
The pathogenesis of chronic inflammation associated with ulcerative colitis with the feared transition to colorectal cancer remains unclear. In the colitic milieu, the stromal fibroblasts may contribute to this transition. Like frankly cancerous fibroblasts, the chemokine, IL8, is secreted by the colitic fibroblasts. Cancer initiating cells from colitis patients express the IL8 receptor, CXCR1. The addition of colitic fibroblasts increased the tumorigenicity of colon cancer initiating cells. Addition of IL8 decreased the tumor latency and increased the growth of colon cancer initiating cells from both colon cancer and colitis. Inhibition of human IL8 diminished the tumorigenicity of colon cancer initiating cells. Blockade of CXCR1 decreases proliferation of colitis-derived spheroid cultures in vitro. Therefore, IL8 represents a potential target to prevent the colitis to carcinoma transition.
aPrincipal Investigator