Expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer. Malignant melanoma as a paradigm.

Evidence is briefly reviewed, primarily in the context of human melanoma, which suggests that acquisition of resistance to multiple, structurally diverse, growth inhibitory cytokines occurs during malignant tumor progression. A similar pleiotrophy appears to occur with respect to growth factor independence. Also discussed is the notion that growth factors that behave as inhibitors for early-stage, benign tumor cells can 'switch' so as to function as mitogens for tumor cells from more advanced stages of disease progression, i.e., when the cells acquire competence for metastasis. The combined phenotypes of 'multicytokine resistance' and 'multi-growth factor independence' help provide tumor cells with the competence to grow in the mesenchymes of the primary organ site and in distant organs.