Modulation of fibronectin production in normal human melanocytes and malignant melanoma cells by interferon-gamma and tumor necrosis factor-alpha.
Normal cultured human epidermal melanocytes and melanoma cells derived from three different malignant melanomas were examined for synthesis of extracellular matrix components before and after treatment for one day with interferon-gamma, tumor necrosis factor-alpha, or both. Treatment of the cells with either cytokine individually had minimal effects on fibronectin levels. Treatment of the cells with the two agents in combination greatly stimulated fibronectin production as indicated by biosynthetic labeling and immunoprecipitation and by enzyme-linked immunosorbent assay. Synthesis of laminin was decreased slightly by the same treatment whereas thrombospondin production was stimulated slightly. The same treatment reduced melanocyte viability slightly but significantly inhibited proliferation and altered the morphology of the melanocytes. The treated cells became flattened and polygonal in shape while the untreated cells exhibited a bipolar shape with one or more long dendritic processes. These morphologic changes were not seen in cultures treated with interferon-gamma or tumor necrosis factor-alpha individually. The effects of interferon-gamma and tumor necrosis factor-alpha on fibronectin production by epidermal melanocytes are in contrast to the effects of the same treatments on fibronectin production by epidermal keratinocytes where fibronectin production is decreased but are similar to the effects of transforming growth factor-beta on a number of other cell types in which increased synthesis of fibronectin occurs and is associated with decreased growth.
Varani
J
J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Mitra
R S
RS
McClenic
B J
BJ
Fligiel
S E
SE
Inman
D R
DR
Dixit
V M
VM
Nickoloff
B J
BJ
D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008545:Melanoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma