A novel mouse model of rectal cancer established by orthotopic implantation of colon cancer cells.
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 x 10(6) 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, mm(3)) 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 (1 x 10(7) 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-intraluminal 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.
Takahashi
Takuya
T
Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo 186-8650, Japan. takuya-takahashi@yakult.co.jp
Morotomi
Masami
M
Nomoto
Koji
K
D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D014183:Transplantation, Heterologous
D000077146:Irinotecan; D002166:Camptothecin