Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA.
Mol Carcinog. 2011 Jan;50(1):58-65. doi: 10.1002/mc.20696.
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.
导致黑色素瘤死亡率的主要因素是其扩散或转移的能力。紫外线 B 光（UVB）被认为是黑色素瘤形成的间接原因。然而，人们对 UVB 对黑色素瘤转移的潜在影响知之甚少。整合素是细胞表面黏附分子（CAM）大家族中的一员，在黑色素瘤细胞的信号转导、生长和迁移过程中起着重要作用。最重要的是，肿瘤细胞的组织浸润依赖于肿瘤细胞与靶器官血管内皮的最初相互作用，越来越多的证据表明黑色素瘤非常晚期抗原-4（VLA-4）整合素与其内皮配体血管细胞黏附分子-1（VCAM-1）的结合在这个过程中起着重要作用。本研究集中于定量调节 UVB 照射后黑色素瘤细胞上 VLA-4 整合素的表达和功能。目前的数据表明，在 UVB 照射后 3、12 和 18 小时，VLA-4 的表达与未处理的细胞相比没有变化，但与 VCAM-1 的黏附显著降低。免疫荧光研究表明，VLA-4 在黑色素瘤细胞表面的空间组织有助于改变 UVB 照射后对 VCAM-1 的亲和力。随着对 UVB 照射下黑色素瘤-内皮相互作用的分子机制的深入了解，可能会开发出治疗黑色素瘤的临床进展。
