UVB-irradiation regulates VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 under flow conditions.
The major aspect contributing to the mortality of melanoma is its ability to spread, or metastasize. Ultraviolet B light (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 (CAMs) 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 very late antigen-4 (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 at 3, 12, and 18 h post-UVB irradiation, VLA-4 expression was unchanged relative to untreated cells, but adhesion to VCAM-1 decreased significantly. Immunofluorescence studies implied that the spatial organization of VLA-4 on the melanoma cell surface contributed to the changes in avidity for VCAM-1 upon UVB irradiation. With increased understanding of the molecular mechanisms underlying melanoma-endothelial interactions upon UVB irradiation, clinical advances for melanoma may be developed.
Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA.
Lei
L
Wang
Venktesh S
VS
Shirure
Monica M
MM
Burdick
Shiyong
S
Wu
D002448:Cell Adhesion / Q000528:radiation effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005455:Fluorescent Antibody Technique; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D014466:Ultraviolet Rays; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1