EXPRESSION OF FIBRONECTIN, FIBRONECTIN ISOFORMS AND INTEGRIN RECEPTORS IN MELANOCYTIC LESIONS

In vitro studies have demonstrated that fibronectin (FN) can deliver a mitogenic signal to quiescent human melanoma cells and that the alpha (5)/beta(1)-integrin receptor mediates this stimulus. In view of this finding we have analysed the in vivo expression of FN, and of ED-A and ED-B FN isoforms, in benign and malignant lesions of melanocyte origi n. In the same specimens the expression of fibronectin integrin recept ors was evaluated. The results demonstrate that, while detection of FN does not correlate with transformation and tumour progression, the ex pression of the two isoforms is associated with transformation and tha t only the ED-A variant is found in metastases. Integrin phenotpping d isclosed that alpha(3)/beta(1) expression is associated with tumour pr ogression, alpha(v)/beta(3) is a marker of transformation, alpha(4) is rarely expressed and alpha(5) is expressed by about 50% and 30% of th e primary and metastatic lesions respectively. Taken together, the res ults of this study demonstrate that transformation and tumour progress ion of the melanocyte lineage are associated with modulation of expres sion of FN isoforms and FN integrin receptors. Furthermore, the expres sion of alpha(5)-integrin in a considerable percentage of primary and metastatic lesions indicates that FN may deliver a proliferative stimu lus to melanoma cells in vivo.