Efficiency of orthotopic xenograft models for human colon cancers

It is feasible to graft human colon cancer tissue into immuno-deficient nude mice, in order to maintain these tumors in vivo. Analysis of the properties tumors under such conditions might increase our knowledge of their biological characteristics. Xenografts are usually implanted into subcutaneous tissue, a site easily accessible for both graft procedure and observation of tumor growth. However these subcutaneous tumors are usually non-invasive and fail to metastasize. To override these limitations we, as others, have tried to improve the tumor xenograft model by transplanting tumors into their original location, designated as the orthotopic site. Transplanted into the cecum of nude mice, human colon cancers were frequently locally invasive and developed liver metastases. These transplantations may be done by injection of colon cancer cell suspensions into the cecal wall. Alternatively, orthotopic implantations of histologically intact tissue were performed and the thus-obtained tumors were more metastatic than tumors obtained after tumor cell injections. The chemosensibility of tumors xenografted into their orthotopic site was different from that of their subcutaneously implanted counterpart. This, added to the enhancement of invasive and metastatic properties, leads us to conclude that colon cancer xenografted into the caecum might be more representative of the clinical situation. We have reviewed the literature and report on the possibilities and limitations different models of colon cancer in vivo.