A novel mouse model of rectal cancer established by orthotopic implantation of colon cancer cells

• Published in: Cancer science 2004-06, Vol.95 (6), p.514-519
• Main Authors: Takahashi, Takuya, Morotomi, Masami, Nomoto, Koji
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Camptothecin; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Carcinoembryonic antigen; Cell Line, Tumor; Chemotherapy; Colitis; Colon cancer; Colorectal cancer; Colorectal carcinoma; Dextran; Dextran sulfate; Disease Models, Animal; Extracellular matrix; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Inflammatory bowel disease; Intestinal microflora; Intestine; Intravenous administration; Invasiveness; Irinotecan; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mucosa; Neoplasm Transplantation; Nodules; Rectal Neoplasms - drug therapy; Rectal Neoplasms - etiology; Rectal Neoplasms - pathology; Rectum; Solid tumors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplantation, Heterologous; Tumor cells; Tumors
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2004.tb03242.x

A novel intraluminal colon tumor model was established in mice by intrarectal instillation of colon cancer cells followed by short term induction of colitis by an irritant agent. Male BALB/c mice were fed a diet containing 3% (w/w) dextran sulfate sodium (DSS) for 7 days to induce colitis, and colon 26 cells (1–2±106 cells/mouse) were infused intrarectally after the mice had been deprived of food for the last 18 h of DSS treatment. The tumor incidence (%) and size (mean volume±SD, mm3) at the rectal mucosa were 35% (2±3), 95% (96±79), 95% (141 ±137) and 94% (325±270) at 1, 2, 3 and 4 weeks after instillation of tumor cells, respectively. Histopathological analyses revealed that a solid tumor was formed initially at the rectal mucosa at 1 week after instillation, then became invasive into the submucosal and muscular tissues at 3 weeks after implantation. Intrarectal instillation of human colon cancer cells, LS174T (1x107 cells/mouse), mixed with “Matrigel” (0±5 mg/mouse), an extracellular matrix solution, in SCID mice led to formation of rectal tumors at 4 weeks after instillation, and immunohistochemical analysis revealed that the tumor cells expressed human carcinoembryonic antigen, suggesting that the tumor nodule was derived from the instilled LS174T cells. Oral or intravenous administration of a camptothecin (CPT) derivative, CPT‐11, resulted in a significant reduction in tumor incidence and tumor volume in the colon 26‐in‐traluminal implantation system. In conclusion, it was suggested that the present intraluminal colon tumor model is useful for examination of chemotherapeutic agents and also intraluminal factors (dietary compounds, intestinal microflora, etc.) that might function to suppress or enhance the growth of colorectal cancer in situ.