Etoh T, Byers H R, Mihm M C
Pathology Department, Harvard Medical School, Massachusetts General Hospital, Boston.
J Dermatol. 1992 Nov;19(11):841-6. doi: 10.1111/j.1346-8138.1992.tb03794.x.
The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of alpha and beta subunits and the beta 1-integrins are especially important as ECM receptors. We investigated the expression of beta 1-integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only alpha 2 beta 1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti-VLA2 monoclonal antibody (mAb). As to FN receptors, alpha 4 beta 1 and alpha 5 beta 1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti-VLA4 and anti-VLA5 mAbs. Our findings provide evidence for a role in beta 1-integrins, in particular alpha 2 beta 1, in melanoma progression and metastasis.
黑色素瘤细胞与细胞外基质（ECM）成分之间的相互作用可能对侵袭和转移至关重要。整合素属于由α和β亚基组成的蛋白质异二聚体家族，其中β1整合素作为ECM受体尤为重要。我们研究了β1整合素在四种人类黑色素瘤细胞系（两种原发性，一种来自放射状生长阶段（RGP），另一种来自垂直生长阶段（VGP），以及两种转移性细胞系）上的表达，并检测了它们在层粘连蛋白（LN）、IV型胶原（CN）和纤连蛋白（FN）上的黏附与迁移情况。在LN和/或CN整合素受体中，与RGP细胞系相比，仅α2β1（VLA2）在VGP和转移性细胞系中的表达水平显著更高。此外，抗VLA2单克隆抗体（mAb）可显著抑制在LN和CN上增强的黏附与迁移。至于FN受体，α4β1和α5β1的表达在各细胞系中存在异质性，然而，其与在FN上增强的黏附与迁移直接相关，这也可被抗VLA4和抗VLA5 mAb抑制。我们的研究结果为β1整合素，尤其是α2β1在黑色素瘤进展和转移中的作用提供了证据。
