Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. Ho wever, less information is available on the potential dynamic changes in ex pression of these molecules on cells during melanoma development and progre ssion in site. Using immunohistochemistry, we tested 40 nevi and primary an d metastatic melanoma lesions for the expression of 10 growth factors and c ytokines and the respective receptors representing 10 cell surface molecule s. Nevi and thin (< 1 mm) primary melanomas showed little expression of lig ands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), tra nsforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivit y of TGF-beta R and c-kit. Marked up regulation of growth factors, cytokine s and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL- 1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SGF), but not IL- 2. Metastases showed similar expression patterns except that SGF was absent . Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF an d IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears t o be a marker of benign lesions; IL-6 and IL-8 expression is associated wit h biologically early malignancy; TGF-beta, GM-CSF and IL-1 alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells util ize cascades of growth factors and cytokines for their progression. Int. J. Cancer (Pred. Oncol.) 84:160-168,1999. (C) 1999 I Wiley-liss, Inc.