ANALYZING THE METASTATIC PHENOTYPE

The dissemination of cells from a primary tumor, resulting in the prog ressive growth of metastatic carcinoma in distant sites, is the most c ommon cause of death of cancer patients. The observations from clinica l studies and the results of experimental studies using rodent tumors and human cancer cells implanted into immunodeficient host animals sug gest that metastasis is not a random event, but rather the result of a sequence of selective events, many of which involve interactions with elements of the microenvironment of the primary and metastatic tumors . Analysis of the metastatic potential of a human tumor cell populatio n has been greatly improved by the introduction of orthotopic models o f tumor growth and metastasis, which have demonstrated that implanting human tumor cells into the appropriate tissue in an immunodeficient r odent can increase both tumor take and incidence of metastasis. These will be the models that should be used to validate the identity of can didate metastasis-associated genes, and to determine the value of new forms of therapy, either genetic or pharmacological, for controlling m etastatic cancer growth. (C) 1994 Wiley-Liss, Inc.