Role of signal transducer and activator of transcription 6 in the development of colitis associated colorectal cancer (TUM7P.959)

Abstract

Abstract STAT6 signaling pathway has important pathophysiologic implications in a variety of cell types and diseases. On cancer studies, mice lacking STAT6 display enhanced tumor immunity to both primary and metastatic mammary carcinomas. In humans, STAT6 protein has been found to be constitutively activated in several cancer types. However, the role of STAT6 in influencing the resistance or susceptibility of colon cancer cells to apoptosis and invasiveness/metastasis has not yet been validated during in vivo colitis-associated colon cancer (CAC).This study aims to identify the effects of STAT6 in tumorigenesis utilizing STAT6-KO mice in an experimental CAC model and evaluating changes in immune cell populations in the absence of this gene. CAC was induced in both STAT6-KO and WT mice by injection of 12.5 mg/kg AOM followed by three rounds of 2% DSS exposure to elicit colitis. On day 63 after CAC induction, mice were sacrificed. Colonic inflammation, proliferation and tumorigenesis were evaluated. Tumor numbers per mouse (0.8 versus 19.6; P=0.0001), and bowel weight (0.3 versus 0.6 g; P=0.05) were significantly decreased in STAT6-KO mice compared to WT mice. Furthermore, both inflammation and proliferation scores in colon from STAT6-KO mice were significantly lower than WT mice. Although additional studies are needed to clarify the mechanism(s) underlying improved anti-tumor immunity in STAT6-KO mice, these results may be a basis for an immunotherapy strategy in CAC development.