Mitogenic activity of laminin on human melanoma and melanocytes: Different signal requirements and role of β1 integrins

R. Mortarini, A. Gismondi, A. Maggioni, A. Santoni, M. Herlyn, A. Anichini

Research output: Contribution to journalArticle

Abstract

The possible mitogenic activity of laminin (LN) on normal and neoplastic 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]thymidine 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 metastasis 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 β1 subunit of VLA integrins and by a combination of mAbs to the α 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 costimulatory activity of immobilized LN for proliferation of melanocytes was observed in the presence of a second signal provided by a set of differed growth factors. The costimulatory activity of LN on melanocytes could be significantly inhibited by mAbs directed to the α and β 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, β1 integrins are differentially involved in the response 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.

Original languageEnglish
Pages (from-to)4702-4710
Number of pages9
JournalCancer Research
Volume55
Issue number20
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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