EXPRESSION AND TOPOGRAPHY OF INTEGRINS AND BASEMENT-MEMBRANE PROTEINS IN EPIDERMAL CARCINOMAS - BASAL BUT NOT SQUAMOUS-CELL CARCINOMAS DISPLAY LOSS OF ALPHA-6-BETA-4 AND BM-600 NICEIN

The expression and topography of some integrins and basement membrane proteins in cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have been studied by immunohistochemistry and Western blotting. it has been shown that the typical cell-to-cell distribution of alpha2beta1 and alpha3beta1 found in normal epidermis is replaced by pericellular distribution in both BCC and SCC cells. BCC and SCC also showed different patterns of expression of alpha6beta4, an integrin heterodimer normally lining the basal surface of basal epidermal keratinocytes: whereas SCC showed high expression and pericellular distribution of alpha6beta4, BCC cells did not express this integrin at all. The absence of alpha6 and beta4 subunits from BCC extracts was confirmed by Western blotting. The molecular composition of the basement membrane was markedly different in the two types of epidermal tumors. Whereas laminin and collagen type IV were conserved in the basement membrane zone of both tumors, the molecular complex BM-600/nicein, which is recognized by the monoclonal antibody GB3 and is possibly identical to the previously described basement membrane glycoproteins kalinin and epiligrin, was absent from BCC cells. Then, the simultaneous loss of expression of alpha6beta4 and BM-600/nicein in BCC cells but not in SCC cells indicates that alpha6beta4 integrin and one of its potential ligands may be co-regulated in both BCC and SCC, thus suggesting a role for this phenomenon in the pathogenesis and clinical behavior of these epidermal tumors.