Alpha-V-dependent outside-in signaling is required for the regulation of CD44 surface expression, MMP-2 secretion, and cell migration by osteopontin in human melanoma cells.
Alpha-V-dependent outside-in signaling is required for the regulation of CD44 surface expression, MMP-2 secretion, and cell migration by osteopontin in human melanoma cells.
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DOI：
10.1016/j.yexcr.2006.03.022
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发表时间：
2006-07
影响因子：
3.7
通讯作者：
V. Samanna;H. Wei;D. Ego-Osuala;M. Chellaiah
中科院分区：
文献类型：
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作者：
V. Samanna;H. Wei;D. Ego-Osuala;M. Chellaiah
整合素αvβ3及其配体骨桥蛋白（OPN）的水平与黑色素瘤和其他癌细胞的致瘤性直接相关。我们之前已经证明，在用可溶性 OPN 处理的黑色素瘤细胞 (M21) 中，与整合素 αvβ3 相关的 pp60c-Srckinase 活性有所增加。在表达缺乏胞质结构域的 αv (αv995) 的黑色素瘤细胞中未观察到 pp60c-Srckinase 活性。目前的研究结果表明，αv 链的 β 转角中的氨基酸序列“995RPPQEEQERE1004”是 pp60c-Src 相互作用所必需的。我们的结果表明，αv 链的 β 转角对于 αv 相关信号复合物的形成和由外向内信号传导可能是不可或缺的。为了进一步分析黑色素瘤细胞中的 αvβ3 信号传导，我们在 M21 细胞 (M21/OPN) 中过表达 OPN。与M21或αv995细胞相比，M21/OPN细胞中条件培养基中的CD44表面表达和MMP-2活性增加到更大程度。此外，M21/OPN 细胞表现出增加的运动性，但在用 αv 和 MMP-2 抑制剂处理后显着降低。我们的研究结果表明，MMP-2 活性的增加是整合素依赖性的，因为在用 αv 抑制剂处理的细胞或表达突变体 αv 的 αv995 细胞中 MMP-2 活性降低。
The level of integrin αvβ3 and its ligand osteopontin (OPN) has been directly correlated to tumorigenicity of melanoma and other cancer cells. We have previously shown an increase in pp60c-Srckinase activity associated with integrin αvβ3 in melanoma cells (M21) treated with soluble OPN. pp60c-Srckinase activity was not observed in melanoma cells expressing αv that lacks the cytoplasmic domain (αv995). Results of the current study demonstrate that the amino acid sequence ‘995RPPQEEQERE1004’ in the β-turn of αv chain is required for the interaction of pp60c-Src. Our results suggest that the β-turn of αv chain may be indispensable for αv-associated signaling complex formation and outside-in signaling. To further analyze the αvβ3 signaling in melanoma cells, we over expressed OPN in M21 cells (M21/OPN). CD44 surface expression and MMP-2 activity in the conditioned medium were increased to a greater extent in M21/OPN cells as compared with M21 or αv995 cells. Also, M21/OPN cells exhibit increased motility, which is markedly reduced upon treatment with inhibitors to αv and MMP-2. Our findings suggest that the increase in MMP-2 activity is integrin-dependent as MMP-2 activity is reduced in cells treated with an inhibitor to αv or in αv995 cells expressing mutant αv.