Alpha 4 integrin increases anoikis of human osteosarcoma cells.
Alpha 4 integrin increases anoikis of human osteosarcoma cells.
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DOI：
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发表时间：
2003
影响因子：
4
通讯作者：
R. Marco;C. Diaz-Montero;J. Wygant;E. Kleinerman;B. McIntyre
中科院分区：
文献类型：
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作者：
R. Marco;C. Diaz-Montero;J. Wygant;E. Kleinerman;B. McIntyre
细胞运动、生长和增殖通过与细胞外基质的粘附来调节。贴壁细胞与细胞外基质的脱离导致细胞凋亡（“失巢凋亡”）的诱导。转化的细胞通常表现出不依赖贴壁的生长，使它们能够获得能动的、侵袭性的表型。这种表型与介导细胞与细胞外基质粘附的跨膜蛋白整合素家族的表达和功能的改变有关。虽然 α4 整合素通常在白细胞亚群上表达，但许多转移性黑色素瘤和肉瘤也表达它。在这项研究中，我们证明了 α4 整合素在人骨肉瘤细胞系 SAOS 以及肺和心包转移性骨肉瘤病变中的表达。我们通过生化分析和使用针对 α4β1 分子独特的组合表位的 mAb 进一步证明 α4 整合素与 β1 亚基偶联。当粘附被拒绝时，SAOS 细胞会发生失巢凋亡。失巢凋亡涉及 caspase 3 的激活和线粒体中细胞色素 c 的释放。用抗 α4 mAb 处理非贴壁 SAOS 会增加失巢凋亡，而抗 β1 整联蛋白 mAb 不会改变失巢凋亡，因此表明 α4 亚基在控制细胞死亡方面具有新功能。由于整合素可以控制细胞迁移、增殖和凋亡，这些结果表明 α4 整合素在骨肉瘤转移的多个方面具有潜在作用。
Cell motility, growth, and proliferation are regulated by adhesion to the extracellular matrix. Detachment of adherent cells from extracellular matrix results in induction of apoptosis ("anoikis"). Transformed cells often show an anchorage-independent growth that enables them to acquire a motile, invasive phenotype. This phenotype has been associated with the altered expression and function of the integrin family of transmembrane proteins that mediate cell adhesion to the extracellular matrix. Although alpha4 integrin is normally expressed on leukocyte subpopulations, a number of metastatic melanomas and sarcomas express it as well. In this study, we demonstrated the expression of alpha4 integrins on the human osteosarcoma cell line SAOS and on metastatic osteosarcoma lesions from the lung and pericardium. We further demonstrated that alpha4 integrin is coupled to the beta1 subunit by biochemical analysis and by using a mAb directed against a combinatorial epitope unique to the alpha4beta1 molecule. SAOS cells undergo anoikis when adherence is denied. Anoikis involved the activation of caspase 3 and the release of cytochrome c from mitochondria. Treatment of non-adherent SAOS with an anti-alpha4 mAb increased anoikis while anti-beta1 integrin mAbs did not alter anoikis, thus indicating a novel function for the alpha4 subunit in the control of cell death. Since integrins can control cell migration, proliferation, and apoptosis these results demonstrate a potential role for alpha4 integrin during multiple aspects of osteosarcoma metastasis.