Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue

Abstract

Nude mice have been used to develop s.c. growing human stomach tumors, but these rarely metastasize. Recently, I. J. Fidler and others have developed orthotopic implantation metastatic models using cell suspensions which are inoculated into the corresponding organ of nude mice from which the tumor cells were originally derived in the human. However, recent work has indicated that disaggregated cell suspensions may not always express their full metastatic potential. In this light, we have recently developed an orthotopic implant model utilizing intact tissue such as that obtained directly from surgery. This approach has yielded high take rates and frequent metastases in colon cancer, bladder cancer, lung cancer, pancreatic cancer, and prostate cancer. We report here the application of this intact tissue orthotopic implant technique to stomach cancer resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject stomach cancer cells at the same site, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of using intact tissue to allow full expression of metastatic potential. Injuring the serosa similar to that occurring in intact tissue transplantation did not increase the metastatic rate after orthotopic injection of cell suspensions of stomach tumor cells. This intact tissue orthotopic implantation model should allow development of new treatment modalities and further study of the biology of human stomach cancer.