The possible mitogenic activity of fibronectin (FN) in human primary and metastatic melanoma lines and clones and the involvement of integrins in mediating this effect were evaluated. Quiescent human melanoma cells cultured in serum-free medium proliferated in a dose- and time-dependent fashion to immobilized FN as indicated by [3H]thymidine incorporation, increment of cell number, and cell cycle analysis. This response to FN was observed with tumor clones isolated from a subcutaneous metastasis and with primary or metastatic melanomas from different patients, but only when tumor cells expressed the α5 subunit of the FN receptor (i.e., VLA-5). Proliferation to FN by a primary tumor (Me4405) expressing all FN receptors and by a tumor clone (2/60) lacking only the α4 subunit was inhibited by monoclonal antibodies to the α5 and β1, but not by monoclonal antibodies to other subunits of FN receptors. Mapping of FN regions responsible for the proliferative signal was performed by stimulating melanoma cells with different FN proteolytic fragments and indicated that a significant mitogenic signal was provided by the Mr 120,000 α-chymotrypsin fragment containing the Arg-Gly-Asp sequence. The proliferation of melanoma cells to FN and to FN fragments was also significantly inhibited by peptides containing the Arg-Gly-Asp sequence. These data indicate that FN can stimulate the proliferation of quiescent melanoma cells and that integrins as α5β1, are involved in the response of tumor cells to this extracellular matrix protein.
|Number of pages||8|
|Publication status||Published - Aug 15 1992|
ASJC Scopus subject areas
- Cancer Research