HETEROGENEITY OF CYTOKINE AND GROWTH-FACTOR GENE-EXPRESSION IN HUMAN-MELANOMA CELLS WITH DIFFERENT METASTATIC POTENTIALS

The purpose of this study was to determine the mRNA expression level o f multiple cytokine and growth factor genes in human malignant melanom a. Melanoma cells were isolated from several surgical specimens, adapt ed to growth in culture, characterized for their ability to produce ex perimental metastases in nude mice, and assessed for cytokine and grow th factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas ana lyzed constitutively expressed steady-state mRNA transcripts for the g rowth and angiogenic factors, basic fibroblast growth factor (bFGF), a nd transforming growth factor or (TGF-alpha), which correlated with me tastatic propensity. Only one highly metastatic melanoma, TXM-1, origi nally isolated from a lymph node metastasis, expressed mRNA transcript s specific for monocyte chemotactic and activating factor (MCAF) and g ranulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, o f the nine melanomas examined, only TXM-1 expressed interleukin (LL)-1 alpha, LL-1 beta, and IL-6, important immunomodulatory cytokines. The se data demonstrate the differential and heterogeneous expression of c ytokine and growth factor genes in human malignant melanoma.