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

Abstract

A novel intraluminal colon tumor model was established in mice by intrarectal instillation of colon cancer cells followed by shortterm 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 × × × ×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. olorectal cancer is one of the leading causes of cancer mortality in the Western world and is also increasing in Japan.1) A great deal of research is currently in progress, not only on treatment, but also on chemoprevention of colon cancer. In order to enable such activity to progress, suitable animal models are required. A heterotopic implantation model has been most widely used to evaluate antitumor agents because of its advantages in practical use, such as high reproducibility, relatively short period needed compared to chemically induced carcinogenic models, and easier technique than other models. 2)However, the heterotopic models have problems in that they are only useful for examination of antitumor/chemopreventive agents with systemic efficacy, 2) and are not suitable for examination of agents/factors that may act in situ.Several animal models produced by orthotopic implantation of colon tumor cells or tissues have been established and utilized to investigate the mechanisms of progression in situ and tumor metastasis, as well as the efficacy of antitumor drugs. [3][4][5][6] In these rodent models, however, either single colon cancer cell suspensions were injected into the submucosal tissues of the cecum or rectum from the serosal aspect [3][4][5] or fragments of colon cancer tissue were sutured to the wall of the colon.6) Implantation by these procedures has been reported to induce colonic tumors in submucosal tissues or growth of tumors at the serosal aspect, but not at the mucosal surface. These animal models therefore appear to be inappropriate to examine the direct influence of the intraluminal environment (dietary components, intestinal microflora, bile acids, etc.) on the growth of colorectal cancers.The objective of this study was therefore to establish an experimental model in which colon tumors are formed at the luminal mucosal surface by instilling colon cancer cells intrarectally in mice. Materials and MethodsAnimals. Male specific-pathogen-free BALB/c mice (9 weeks old) and male C.B-17 SCID mice (scid/scid, 6 weeks old) were purchased from Japan SLC Inc. (Hamamatsu) and CLEA Japan, Inc. (Tokyo), respec...

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