Development of a highly liver metastatic animal model of human gastric carcinoma in nude mice : correlation between liver metastatic potential and tumorigenicity

Abstract

Background and aim: To establish a nude mice model of human gastric carcinoma via the intrasplenic inoculation of histologically intact tissue and to study the in vivo correlation between liver metastasis and tumorigenicity of a gastric cancer cell line.Materials and Methods: For a liver metastasis model, 10,000,000 viable cells of the human gastric cancer cell line MKN-28 were injected into the spleen subcapsule of each of the 4 SLC nude mice. After observation during the period of 5 to 25 weeks, mice that had developed liver metastatic tumors were collected from groups. Then, the primary tumor was cultured with RPMI 1640 and resuspended in the same medium. Single cell suspension of 10,000,000 cells was injected into the spleen subcapsule of each of another 4 mice, successively. The cells of MKN-28 and its successive passage cell lines were inoculated into each of the spleen subcapsules of 4 mice and the selection cycle was repeated 4 times to yield an original cell line designated as MKN-28LM-4P, to determine their tumorigenicity, and a tumor volume was measured every 4 days after inoculation.Results: MKN-28 injected mice developed hematogenous metastasis and they were clinically manifested as cachexia. Metastatic lesions were mostly noted in the liver. The incidences of the liver metastasis was MKN-28: 2/4(50%), MKN-28LM-1P: 1/4(25%), MKN-28LM-2P: 3/4(75%), MKN-28LM-3P: 4/4(100%), and MKN-28LM-4P: 4/4(100%). MKN-28LM-4P shows a high rate of metastasis to the liver of nude mice. All of the inoculated nude mice showed significant tumor mass growth. A tumor formed by MKN-28-4P cells grew significantly more rapidly compared to a tumor formed by the original MKN-28 cells in mice.Conclusion: The model of nude mice with the transplantation of histologically intact gastric cancer tissue by intrasplenic injection is an ideal model to study the biologic features of hepatic metastatic gastric cancer in vivo and to explore the mechanisms of carcinogenesis and clinical treatment strategies.