Patient-Like Orthotopic Metastatic Models of Human Cancer

Abstract

In 1889, Paget formulated the seed and soil hypothesis of cancer metastasis. Since that time there have ben major efforts to develop animal models of cancer to test and investigate the hypothesis of Paget as well as for treatment and drug discovery. Thus, there has been a critical need in cancer treatment and research for rodent models that are clinically relevant. Ideal models would allow the transplantation of the majority of human tumors such that the tumor would behave in the rodent in a similar manner as it did in the patient. Such models would be useful for individual patient treatment design and for evaluation of new antineoplastic agents and procedures. This review traces the development of rodent animal models from the first transplantation experiments over 100 yr ago to the present era. The present era is one of great promise, with the use of immunodeficient rodents, which accept foreign tissues for human tumor transplantation. The modern era is characterized by new orthotopic transplant methodologies that allow human tumors to express their metastatic potential, especially the models developed in our laboratory that are constructed by surgical orthotopic implantation with intact tumor tissue. The use of tumors expressing green fluorescent protein and other fluorescent proteins for external whole-body imaging has enabled imaging of tumor growth and metastasis even on internal organs. The SOI models have allowed experimental confirmation of Paget’s seed and soil hypothesis of 1889. The use of SOI models for discovery of antimetastatic and antiangiogenesis agents is discussed. The exciting possibility of the use of the SOI models for discovery of antitumor and antimetastatic genes is also discussed.