EXPRESSION OF E-CADHERIN AND P-CADHERIN BY MELANOMA-CELLS DECREASES IN PROGRESSIVE MELANOMAS AND FOLLOWING ULTRAVIOLET-RADIATION

The purpose of our study was to determine whether the degree of E- and P-cadherin expression in melanomas correlates with the invasive behav ior of the clinical lesions from which the cell lines were derived, Ca dherins comprise a family of calcium-dependent cellular adhesion molec ules expressed on most cell types that form solid tissues, In the huma n epidermis, melanocyte cadherin expression may function to maintain t he integrity of the epidermal-melanin unit, Employing both immunofluor escence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma ce ll lines derived from primary or metastatic lesions using the monoclon al antibodies HECD-1 and NNC-CAD-299, respectively, Human epidermal me lanocytes isolated from neonatal foreskin were evaluated by similar te chniques and served as a biologic control. Melanoma cell lines were is olated from primary or metastatic lesions of patients described as hav ing ''early,'' ''intermediate,'' or ''advanced disease.'' Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activ ated cell sorter, varied inversely with disease progression, Selected log mean ratios of E-cadherin fluorescence, as compared to human epide rmal melanocytes (arbitrarily 1), ranged from 1.04 in the WM 35 melano ma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A a nd 1361A melanoma cell lines (derived from primary lesions with metast ases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced dise ase was observed, Melanoma cells appear to express E- and P-cadherin l evels inversely related to disease progression, Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epid ermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin e xpression in the WM 35 melanoma cell line decreased substantially. Thu s, ultraviolet radiation may have a direct effect on human epidermal m elanocytes and melanoma cell attachment through cadherins within the e pidermis or tumor nodules.