UVB Irradiation on Melanoma Cells Regulates α4β1 Integrin (VLA‐4) Avidity for Its Ligand VCAM‐1

Abstract

The major aspect contributing to the mortality of melanoma is its ability to spread, or metastasize. Ultraviolet light B (UVB) is considered an indirect cause of melanoma formation. However, little is known about the potential effects of UVB to melanoma metastasis. Integrins, a large family of cell adhesion molecules expressed on the melanoma cell surface, are important for cell signaling, growth, and migration during metastasis. Most critically, tumor cell tissue invasion is dependent on the initial interaction of tumor cells with vascular endothelium at the target organ, and there is increasing evidence for a prominent role of melanoma VLA‐4 integrin binding to its endothelial ligand vascular cell adhesion molecule‐1 (VCAM‐1) in this process. This research focuses on the quantitative modulation of VLA‐4 integrin expression and function on melanoma cells after UVB irradiation. The present data show that 3 hours post‐UVB irradiation, VLA‐4 expression was unchanged relative to untreated cells, but adhesion to VCAM‐1 decreased ~70%. At 12 hours post‐treatment, VLA‐4 expression was reduced to ~50% of untreated cells, yet adhesion to VCAM‐1 was similar to the 3‐hour time point. Further studies imply that the spatial organization of VLA‐4 in the melanoma membrane contributes the changes in avidity for VCAM‐1. Understanding of the molecular mechanism underlying melanoma‐endothelia interactions upon UVB irradiation can guide the development of clinical advances for melanoma.