Active transforming growth factor-beta in human melanoma cell lines: no evidence for plasmin-related activation of...

Cultured human melanoma cells were found to secrete TGF-beta mostly in latent biologically inactive form but in addition five of six melanoma cell lines studied produced in conditioned culture medium active TGF-beta in the range from 370 to 610 pg per 10(6) cells per 24 h. A distinct characteristic of these melanoma cell lines is that they form active surface-bound plasmin by the activation of plasminogen with surface-bound tissue-type plasminogen activator. The present study was performed to assess the role of plasmin in the process of latent TGF-beta activation in the melanoma cell lines. No direct correlation was found between cell-associated plasmin activity and the amount of active TGF-beta present in the conditioned medium of individual cell lines. The melanoma cell lines exhibited diverse responses to exogenous active TGF-beta 1; three cell lines were growth-stimulated, two were growth-inhibited, and one had a very low sensitivity to the growth factor. The active TGF-beta produced by the melanoma cells was found to inhibit the natural killer cell function of peripheral blood lymphocytes, suggesting that it may have an immunosuppressive effect and a role in the development of melanomas.