Metastases of human tumors in experimental animals

A large variety of models of both artificial and spontaneous metastases have been developed in experimental animals. These models have enabled the characterization of metastatic cancer cells and have helped in understanding the metastatic process. Studies of experimental metastases of human tumors have so far been rather limited; these have been developed by xenografting human tumors in immuno-compromised animals, especially athymic nude mice. Although nude mice only seldom develop metastases when grafted with human tumor cells, the selection of human cancer cells with increased metastatic abilities could be obtained in a number of cases. Human melanoma variants and clones with increased metastatic abilities were obtained from melanoma cell lines in nude mice and in immunosuppressed newborn rats. Subcutaneous transplantation in a nude mouse of a human melanoma metastatic nodule resulted in a subcutaneous tumor (NTT) and in spontaneous lung (NTP) and lymph node (NTG) metastases which were first maintained in vivo by subcutaneous passages in nude mice and then cultured in vitro as cell lines. Cytogenetic studies showed that all three tumor lines have a common origin and that metastases resulted from a population selection. After 15 in vitro passages, NTP cells were reinjected s.c. in nude mice: serial transplantation was accompanied by an increase in metastatic abilities of tumor cells. Melanoma cell lines, tumorigenic but non metastatic in nude mice were xenografted to ATS-treated newborn rats. 3 weeks after s.c. injection of 10(6) cells, nearly all rats developed tumors and a proportion of them lung and lymph node metastases. Agar cloning of M4Beu line showed that it is heterogeneous and contains poorly tumorigenic but highly metastatic cells. In addition, serial in vivo passages resulted in the selection of highly tumorigenic but poorly metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)