Rapid development of hepatic metastasis with high incidence following orthotopic transplantation of murine colon 38 carcinoma as intact tissue in syngeneic C57BL/6 mice.
OBJECTIVE
Orthotopic transplantation of human colon tumors was a useful method for producing hepatic metastasis in mice. In many cases, however, it took about 3 months for evaluation. We examined an in vivo model of hepatic metastasis for only 4 weeks by conducting orthotopic transplantation of murine Colon 38 tumor using intact tissue in syngeneic mice and determined the efficacy of chemotherapeutic agents against hepatic metastasis.


METHODS
Twenty milligrams of tumor tissues were prepared from subcutaneously (s.c.) growing Colon 38 tumor and orthotopically transplanted on the cecum in C57BL/6 mice. Mice were autopsied about 4 weeks after transplantation. Metastases to various organs were detected macroscopically or histochemically and tumor invasion into the cecum was observed histochemically. In experimental chemotherapy, mice bearing orthotopically transplanted Colon 38 tumor were separated into three equal groups and were either treated with fluorouracil or cisplatin (CDDP), or untreated. Four weeks after transplantation, activities of both agents against local tumor growth and hepatic metastasis were evaluated.


RESULTS
Macroscopic metastases to various organs including the liver, the lung, and the peritoneum were developed during days 28 to 32 after inoculation. The frequency of hepatic metastasis was 96% (N = 23). Histological examination indicated that the local tumor invaded various layers of the cecum and metastasized to the liver and lung hematogenously. In experimental chemotherapy with fluorouracil and CDDP, only fluorouracil decreased the incidence of mice with hepatic metastasis (2/8 cases), compared with vehicle treatment (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%; mean tumor weight of the test group (T) compared with that of the control group (C)] was similar to that of fluorouracil (53%).


CONCLUSIONS
This model, with its rapid development of hepatic metastasis in high frequency, should be useful as a screening assay to find anti-metastatic agents for colorectal carcinoma.
Funahashi
Y
Y
Tsukuba Research Laboratories, Eisai Co. Ltd., Ibaraki, Japan. y1-funahashi@eisai.co.jp
Koyanagi
N
N
Sonoda
J
J
Kitoh
K
K
Yoshimatsu
K
K
D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000556:secondary; D014185:Transplantation, Isogeneic
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil