Roberta Mortarini , Angela Gismondi , Andrea Maggioni , et al . Integrins 1 β Melanocytes : Different Signal Requirements and Role of Mitogenic Activity of Laminin on Human Melanoma and Updated

The possible mitogenic activity oflaminin (LN) on normal and neoplas tic cells of the melanocyte lineage was tested by culturing growth-arrested human melanoma cells and neonatal foreskin melanocytes on LN. Serum deprived, quiescent melanoma cells proliferated, in serum-free medium, in a dose-dependent fashion to immobilized LN as determined by [3H]thy midine incorporation, cell cycle analysis, and change in cell number. The mitogenic activity of LN on melanoma cells was not mediated through autocrine release of growth factors and was observed with primary or metastatic melanoma cells and with clones isolated from the same metas tasis but only on cells expressing very late antigen (VLA).3 and VLA-6 laminin receptors. Proliferation of melanoma cells to LN was significantly inhibited by a mAb to the @31 subunit of VLA integrins and by a combi nation of mAbs to the a subunits of VLA-3 and VLA-6. By contrast, LN did not act as a mitogen on human melanocytes expressing VLA-3 and VLA-6 and cultured in serum-free medium. However, a cosfimulatory activity of immobilized LN for proliferation of melanocytes was observed in the presence of a second signal provided by a set of different growth factors. The costimulatory activity of LN on melanocytes could be signif icantly Inhibited by mAbs directed to the a and @3 chain of VLA-6 but not to VLA-3. These data suggest that LN itself, and not growth factors possibly associated with it, can exert a mitogenic activity on quiescent human melanoma cells and that a change in the signal requirements for response to LN occurs upon neoplastic transformation in the melanocyte lineage. Furthermore, @31 integrins are differentially involved in the re sponse of the normal and the neoplastic cells to LN, since VLA-3 and VLA-6 cooperate in the proliferation of neoplastic cells, while VLA-6 is relevant for the response of melanocytes.