Integrin expression regulates neuroblastoma attachment and migration
Integrin expression regulates neuroblastoma attachment and migration
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DOI：
10.1593/neo.03445
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发表时间：
2004-07-01
期刊：
影响因子：
4.8
通讯作者：
Feldman, EL
中科院分区：
文献类型：
--
作者：
Meyer, A;van Golen, CM;Feldman, EL
神经母细胞瘤(NBL)是婴幼儿最常见的恶性肿瘤，儿童骨转移死亡率高达90%以上。两类主要的蛋白质，整合素和生长因子，调节转移过程。我们先前已经证明，致瘤的NBL细胞表达较高水平的I型胰岛素样生长因子受体(IGF-IR)，并且整合素的表达与NBL的致瘤潜力成反比。在本研究中，我们分析了整合素和IGF-IR对NBL细胞黏附和迁移的影响。非致瘤性S细胞表达高水平的β(1)整合素，而致瘤性N细胞表达很少的β(1)整合素。β(1)整合素的改变是由于蛋白质水平的调节，因为在N型细胞中翻译减少。此外，对蛋白质合成的抑制表明，在S型细胞(SHEP)中，β(1)整合素的降解速度比在N型细胞(SH-SY5Y和IMR32)中要慢。抑制α(5)β(1)整合素可阻止Shep(但不能阻止SH-SY5Y或IMR32)细胞与纤维连接蛋白的附着，并增加Shep细胞的迁移。IGF-IR的增加降低了β(1)整合素的表达，并可能通过增加α(V)β(3)的表达来增强Shep细胞的迁移。这些数据表明，特定类别的整合素与IGF-IR共同调节NBL的附着和迁移。
Neuroblastoma (NBL) is the most common malignant disease of infancy, and children with bone metastasis have a mortality rate greater than 90%. Two major classes of proteins, integrins and growth factors, regulate the metastatic process. We have previously shown that tumorigenic NBL cells express higher levels of the type I insulin-like growth factor receptor (IGF-IR) and that, integrin expression is inversely proportional to tumorigenic potential in NBL. In the current study, we analyze the effect of, integrin and IGF-IR on NBL cell attachment and migration. Nontumorigenic S-cells express high levels of beta(1) integrin, whereas tumorigenic N-cells express little beta(1) integrin. Alterations in beta(1) integrin are due to regulation at the protein level, as translation is decreased in N-type cells. Moreover, inhibition of protein synthesis shows that beta(1) integrin is degraded more slowly in S-type cells (SHEP) than in N-type cells (SH-SY5Y and IMR32). Inhibition Of alpha(5)beta(1) integrin prevents SHEP (but not SH-SY5Y or IMR32) cell attachment to fibronectin and increases SHEP cell migration. Increases in IGF-IR decrease beta(1) integrin expression, and enhance SHEP cell migration, potentially through increased expression Of alpha(v)beta(3). These data suggest that specific classes of integrins in concert with IGF-IR regulate NBL attachment and migration.