According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC-min mouse correspondingly is a widely used model for the study of this type of cancer. Studies indictate that the matricellular protein Thrombospondin 1 (TSP1) is lost during progression of colon cancer. To study the role of TSP1 in this disease we generated APC-min and TSP-/- APC-min mice. Our data indicates that expression of TSP1 in the APC-min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. On the other hand lack of TSP1 increases tumor multiplicity in these mice, and up-regulates Ki67 in intestinal tissue. Moreover TSP-/- APC-min mice show 50% reduction in survival when compared to TSP+/+APC-min mice alone. Here we show that ADD1/SREBP1 a key transcription factor linking changes in nutritional status of certain genes that regulate systemic energy metabolism is upregulated only in the TSP null APC min/+ animals indicating and association with increased tumor aggressiveness. Together this data indicates that TSP1 regulates progression of colon carcinogenesis and define molecular targets of TSP1 in the prevention of colorectal cancer.
Citation Format: David R. Soto Pantoja, Maria E. Torres, J. Michael Sipes, Nicole Morris, David D. Roberts, Nancy J. Emenaker. Thrombospondin-1 regulates carcinogenesis in an in vivo model of colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B18.