Many if not most gastrointestinal cancers arise in the setting of chronic inflammation, and examples include gastroesophageal reflux-induced esophageal adenocarcinoma, H. pylori-associated gastric cancer and colitis-associated colorectal cancer. We have utilized murine models of esophagitis (L2-IL-1β transgenic mice), gastritis (H/K-ATPase-IL-1β and Helicobacter felis infection) and colitis (AOM/DSS) to investigate the role of chronic inflammation in the development of malignancy. In models of chronic gastrointestinal inflammation, there is an early expansion of immature myeloid cells (IMC) followed later by increases in αSMA+ stromal fibroblasts (CAFs). The increase in IMC results from in part from an expansion of splenic progenitors/HSC, while the increased CAFs reflects an increase in mesenchymal stem cells (MSCs) within the preneoplastic tissue. Together, the amplification of myeloid progenitors and MSC-derived stromal cells results in an evolving cancer niche that contributes to expansion of gut progenitors. In the colon, these inflammatory signals can results in crypt fission and monoclonal conversion of intestinal crypt units. Thus, an early amplification of epithelial stem or progenitor cells appears to be a requirement for the development of neoplasia. Eliminating the early cancer niche, which appears to be needed for the initiation of tumors, appears to represent a potential strategy for cancer prevention.

Citation Format: Timothy C. Wang. Inflammation, stem cells, and cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PL02-01.