Keratinocytes express the CD146 (Muc18/S-Endo) antigen in tissue culture and during inflammatory skin diseases

The CD146 (or MUC18/MEL-CAM) antigen is a cell adhesion molecule of the imm unoglobulin superfamily. Besides in melanoma, expression of CD146 antigen h as been demonstrated in breast epithelia and hair follicles. We studied its expression by human keratinocytes in culture as well as in neoplastic and inflammatory skin diseases. Staining of primary cultured keratinocytes reve aled expression of CD146 on the cell membrane, preferentially on cell-cell contact sites. Western blot analysis of keratinocytes detected a band of ap proximate to 113 kDa, corresponding to the CD146 protein. In contrast to pr imary keratinocytes, neither CD146 protein nor mRNA expression was found in the keratinocyte-derived cell lines A431 and HaCaT. Treatment of keratinoc ytes with the proinflammatory cytokines interleukin-1 and interleukin-6, tu mor necrosis factor-alpha, and interferon-gamma, resulted in no change of C D146 expression and incubation with phorbol 12-myristate 13-acetate led to a reduction of CD146 on keratinocytes. By contrast, when culturing keratino cytes in medium devoid of growth supplements, a distinct upregulation was o bserved as compared with culture in fully supplemented medium. In normal hu man epidermis expression of the CD146 antigen was not detectable. It was st rongly upregulated, however, on suprabasal keratinocytes in psoriasis, in l ichen planus, in the epidermis overlying skin neoplasms, and in viral warts . In squamous cell carcinomas and basal cell carcinomas only a minority of tumor cells expressed CD146. Our findings suggest that the CD146 antigen re presents an activation marker of keratinocytes and may be involved in cutan eous inflammatory tissue reaction.