1. Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju, Wonju, Gangwon-do 26493, Republic of Korea
2. Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, 26426, Republic of Korea
3. Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea
4. Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea
5. Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, U.S.A.
The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer. The human commensal bacterium, enterotoxigenic Bacteroides fragilis (ETBF) secretes the Bacteroides fragilis toxin (BFT) which is necessary and sufficient to cause colitis. We report that BALB/c mice infected with WT-ETBF and administered three cycles of AOM/DSS developed numerous, large-sized polyps predominantly in the colorectal region. In addition, AOM/DSS-treated BALB/c mice orally inoculated with wild-type nontoxigenic Bacteroides fragilis (WT-NTBF) overexpressing bft (rETBF) developed numerous polyps whereas mice infected with WT-NTBF overexpressing a biologically inactive bft (rNTBF) did not promote polyp formation. Unexpectedly, the combination of AOM+ETBF did not induce polyp formation whereas ETBF+DSS did induce polyp development in a subset of BALB/c mice. In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.
Keywords: ETBF, colorectal cancer, inflammation, azoxymethane, dextran sulfate sodium