Rapid development of hepatic metastasis with high incidence following orthotopic transplantation of murine colon 38 carcinoma as intact tissue in syngeneic C57BL/6 mice

Background and Objectives: Orthotopic transplantation of human colon tumors was a useful method for producing hepatic metastasis in mice. In many case s, however, it took about 3 months for evaluation. We examined an in vivo m odel of hepatic metastasis for only 4 weeks by conducting orthotopic transp lantation of murine Colon 38 tumor using intact tissue in syngeneic mice an d determined the efficacy of chemotherapeutic agents against hepatic metast asis. Methods: Twenty milligrams of tumor tissues were prepared from subcutaneous ly (s.c.) growing Colon 38 tumor and orthotopically transplanted on the cec um in C57BL/6 mice. Mice were autopsied about 4 weeks after transplantation . Metastases to various organs were detected macroscopically or histochemic ally and tumor invasion into the cecum was observed histochemically. In exp erimental chemotherapy, mice bearing orthotopically transplanted Colon 38 t umor were separated into three equal groups and were either treated with fl uorouracil or cisplatin (CDDP), or untreated. Four weeks after transplantat ion, activities of both agents against local tumor growth and hepatic metas tasis were evaluated. Results: Macroscopic metastases to various organs including the liver, the lung, and the peritoneum were developed during days 28 to 32 after inoculat ion. The frequency of hepatic metastasis was 96% (N = 23). Histological exa mination indicated that the local tumor invaded various layers of the cecum and metastasized to the liver and lung hematogenously. In experimental che motherapy with fluorouracil and CDDP, only fluorouracil decreased the incid ence of mice with hepatic metastasis (2/8 cases), compared with vehicle tre atment (7/8 cases) and the number of metastatic nodules in the liver (P = 0 .016), although the inhibition against local growth of CDDP in T/C [45%; me an tumor weight of the test group (T) compared with that of the control gro up (C)] was similar to that of fluorouracil (53%). Conclusions: This model, with its rapid development of hepatic metastasis i n high frequency, should be useful as a screening assay to find anti-metast atic agents for colorectal carcinoma. J. Surg. Oncol. 1999;71:83-90. (C) 19 99 Wiley-Liss, Inc.