ROLE OF THE ALPHA-V-BETA-3 INTEGRIN IN HUMAN-MELANOMA CELL INVASION

ROLE OF THE ALPHA-V-BETA-3 INTEGRIN IN HUMAN-MELANOMA CELL INVASION
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DOI:
10.1073/pnas.89.5.1557
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发表时间:
1992-03-01
影响因子:
11.1
通讯作者:
HENDRIX, MJC
HENDRIX, MJC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SEFTOR, REB;SEFTOR, EA;HENDRIX, MJC

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人黑色素瘤细胞系A375 M在其细胞表面上表达玻连蛋白受体(α(v)β-3整联蛋白)。用多克隆或单克隆抗α(v)β-3抗体处理A375 M细胞,导致体外刺激通过基底膜基质的侵袭。用单克隆抗α(v)抗体对这些细胞进行类似的处理,其不抑制α(v)β-3抗原的粘附功能,也刺激了侵袭;然而,抗β-3抗体处理没有效果。此外,用玻连蛋白预处理细胞或将玻连蛋白添加到基底膜基质中也导致了侵袭的刺激。用纤连蛋白受体抗体或纤连蛋白类似的处理对侵袭没有影响。用抗α(v)β-3抗体处理的细胞中IV型胶原酶表达的分析显示分泌的72-kDa酶及其mRNA的水平更高。通过α(v)β 3整合素的信号转导可能是金属蛋白酶表达升高和A375 M细胞通过基底膜基质侵袭增强的基础。
The human melanoma cell line A375M expresses the vitronectin receptor (alpha(v)beta-3 integrin) on its cell surface. Treatment of A375M cells with either polyclonal or monoclonal anti-alpha(v)beta-3 antibodies resulted in stimulation of invasion through basement membrane matrices in vitro. Similar treatment of these cells with a monoclonal anti-alpha(v) antibody, which does not inhibit the adhesive function of the alpha(v)beta-3 antigen, also stimulated invasion; however, anti-beta-3 antibody treatment had no effect. Furthermore, pretreatment of the cells with vitronectin or addition of vitronectin to the basement membrane matrix also resulted in stimulation of invasion. Similar treatments with fibronectin receptor antibody or fibronectin had no effect on invasion. Analysis of type IV collagenase expression in cells treated with anti-alpha(v)beta-3 antibody showed higher levels of both the secreted 72-kDa enzyme and its mRNA. Signal transduction through the alpha(v)beta-3 integrin could underlie the elevated expression of metalloproteinase and the enhanced invasion of A375M cells through basement membrane matrices.