Transforming growth factor beta 1 induces apoptosis in normal melanocytes but not in nevus cells grown in type I collagen gel

We used type I collagen gel cultures to compare the growth requirements of melanocytes and dermal nevus cells. Melanocytes but not nevus cells undergo apoptosis in collagen unless supplied with growth stimulators such as fibr oblast growth factor 2. To characterize the mechanism of melanocyte apoptos is in collagen, we tested the effects of transforming growth factor beta 1, known to be functionally active in the skin. When picomolar amounts of tra nsforming growth factor beta 1 were added to normal melanocytes grown in ty pe I collagen gel, their apoptosis was dramatically accelerated. In contras t, the apoptotic rate of nevus cells and melanoma cells grown under similar conditions was not affected by transforming growth factor beta 1. The incr eased apoptosis of normal melanocytes was effectively counteracted by addit ion of either neutralizing transforming growth factor beta 1 antibodies or fibroblast growth factor 2 to the collagen gel. Interestingly, the backgrou nd apoptosis of normal melanocytes was also inhibited by transforming growt h factor beta 1 antibodies. By Western blotting we detected transforming gr owth factor beta-like immunoreactivity in melanocyte, nevus cell, and melan oma cell lysates. A sensitive bioassay confirmed that their medium containe d considerable amounts of heat-activatable growth inhibitory activity that could partly be neutralized by transforming growth factor beta 1 antibodies . It is evident that apoptosis of melanocytes grown in type I collagen gel can be mediated by both endogenous and exogenous transforming growth factor beta. We suggest that the balance between inhibitory growth factors such a s transforming growth factor beta and stimulatory growth factors like fibro blast growth factor 2 has the potential to regulate the growth, localizatio n, and survival of normal melanocytes also in vivo. The resistance of nevus cells to transforming-growth-factor-beta-mediated apoptosis may facilitate their ability to grow in the dermal compartment of the skin.