van Leeuwen R L, Yoshinaga I G, Akasaka T, Dekker S K, Vermeer B J, Byers H R
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Exp Dermatol. 1996 Dec;5(6):308-15. doi: 10.1111/j.1600-0625.1996.tb00134.x.
Recent in situ studies suggest the alpha V beta 3 integrin is a tumour progression marker in melanoma. We analyzed 5 human melanoma cell lines for their expression of the vitronectin binding alpha V beta 3 and alpha V beta 5 integrins using flow cytometry. The role of these receptors in cell attachment, spreading and migration was investigated using attachment assays, video time lapse spreading and migration assays and with function blocking monoclonal antibodies. Cell lines derived from later stages of tumor progression exhibited high levels of alpha V beta 3 expression, whereas no similar correlation with alpha V beta 5 expression was identified. Cell attachment, spreading and migration response on vitronectin correlated well with the expression level of the alpha V beta 3 but not the alpha V beta 5 vitronectin receptor. Blocking of the alpha V beta 3 integrin resulted in a significant decrease in cell attachment, spreading and motility whereas the function blocking antibody against the alpha V beta 5 integrin only inhibited cell attachment in cell lines with the highest level of expression of this integrin. Taken together, our study indicates that the level of expression of the alpha V beta 3 and alpha V beta 5 integrins is heterogeneous in melanoma cell lines and that the alpha V beta 5 integrin, if present, may function only during the initial cell attachment whereas the alpha V beta 3 plays an important role in cell spreading and cell migration as well.
近期的原位研究表明,αVβ3整合素是黑色素瘤中的一种肿瘤进展标志物。我们使用流式细胞术分析了5种人类黑色素瘤细胞系中玻连蛋白结合性αVβ3和αVβ5整合素的表达情况。使用细胞附着试验、视频延时铺展和迁移试验以及功能阻断单克隆抗体,研究了这些受体在细胞附着、铺展和迁移中的作用。源自肿瘤进展后期的细胞系表现出高水平的αVβ3表达,而未发现与αVβ5表达有类似的相关性。细胞在玻连蛋白上的附着、铺展和迁移反应与αVβ3的表达水平密切相关,而与αVβ5玻连蛋白受体的表达水平无关。阻断αVβ3整合素会导致细胞附着、铺展和运动能力显著下降,而针对αVβ5整合素的功能阻断抗体仅在该整合素表达水平最高的细胞系中抑制细胞附着。综上所述,我们的研究表明,αVβ3和αVβ5整合素在黑色素瘤细胞系中的表达水平是异质性的,并且αVβ5整合素(如果存在)可能仅在细胞初始附着过程中起作用,而αVβ3在细胞铺展和细胞迁移中也起着重要作用。