Expression of E 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 behavior of the clinical lesions from which the cell lines were derived. Cadherins comprise a family of calcium-dependent cellular adhesion molecules expressed on most cell types that form solid tissues. In the human epidermis, melanocyte cadherin expression may function to maintain the integrity of the epidermal-melanin unit. Employing both immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma cell lines derived from primary or metastatic lesions using the monoclonal antibodies HECD-1 and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal foreskin were evaluated by similar techniques and served as a biologic control. Melanoma cell lines were isolated from primary or metastatic lesions of patients described as having "early," "intermediate," or "advanced disease." Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell sorter, varied inversely with disease progression. Selected log mean ratios of E-cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily = 1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary lesions with metastases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced disease was observed. Melanoma cells appear to express E- and P-cadherin levels inversely related to disease progression. Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epidermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin expression in the WM 35 melanoma cell line decreased substantially. Thus, ultraviolet radiation may have a direct effect on human epidermal melanocytes and melanoma cell attachment through cadherins within the epidermis or tumor nodules.