Selective down-regulation of the α6-integrin subunit in melanocytes by UVB light

In vivo, melanocytes bind to laminin (LM) molecules of the basement membrane (BM) via the integrins alpha 3 beta 1 and alpha 6 beta 1, and they adhere to neighbouring keratinocytes via E-cadherin. Only few studies have addressed the impact of ultraviolet (UV) light on the interaction of melanocytes with their microenvironment. In this report, we examined the influence of UVB irradiation on the expression of the most important melanocyte-adhesion molecules (E-, N-cadherin, alpha 2-, alpha 3-, alpha 5-, alpha 6-, alpha V-, beta 1-, beta 3-integrins and ICAM-1) in vitro by flow cytometry. We were able to demonstrate that the alpha 6-integrin subunit is selectively and reversibly down-regulated by UVB in a dwzm 150ose-dependent manner. In comparison, keratinocytes lacked UVB-inducible alterations in the expression of alpha 6-integrin. In the presence of LM-1, the UVB-induced down-regulation of alpha 6-integrin in melanocytes was significantly reduced. Moreover, LM-1 increased the resistance of melanocytes to UVB-induced cell death, as measured by annexinV-binding analysis. This effect was reversed by preincubation with an alpha 6-integrin-blocking antibody. By immunofluorescence, we could demonstrate that UVB leads to a dose-dependent internalization of alpha 6-integrin, providing an obvious explanation for the down-regulation on the outer cell surface observed by flow cytometry. We suggest that adhesion to LM-1 through alpha 6-integrin represents a protective mechanism for melanocytes to withstand UVB damage. Through alpha 6-integrin internalization, sunburns might alter the interaction between melanocytes and the BM, resulting in apoptosis induced by loss of anchorage (anoikis). Repeated sunburns may then lead to the selection of a population of melanocytes which are capable of anchorage-independent survival, culminating in solar nevogenesis and melanoma development.