CCN6 Enhances ICAM-1 Expression and Cell Motility in Human Chondrosarcoma Cells
CCN6 Enhances ICAM-1 Expression and Cell Motility in Human Chondrosarcoma Cells
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DOI：
10.1002/jcp.22720
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发表时间：
2012-01-01
影响因子：
5.6
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Fong, Yi-Chin;Lin, Chih-Yang;Tang, Chih-Hsin
软骨肉瘤是一种高度恶性的肿瘤，具有强大的局部侵袭能力并引起远处转移。软骨肉瘤显示出转移到肺部的倾向。CCN 6是一种富含半胱氨酸的蛋白质，属于CCN（Cyr 61，CTGF和Nov）家族的基质细胞蛋白质。然而，CCN 6对人类软骨肉瘤细胞的影响在很大程度上是未知的。在这项研究中，我们发现CCN 6增加了人软骨肉瘤细胞的迁移和细胞间粘附分子-1（ICAM-1）的表达。α v β 3和α v β 5整合素单克隆抗体和丝裂原活化蛋白激酶（MEK）抑制剂（PD 98059和U 0126）抑制CCN 6诱导的软骨肉瘤细胞迁移和ICAM-1上调。CCN 6刺激增加了黏着斑激酶（FAK）、MEK和细胞外信号调节激酶（ERK）的磷酸化。此外，激活蛋白-1（AP-1）抑制剂抑制CCN 6增强的细胞迁移和ICAM-1表达。此外，CCN 6增加AP-1荧光素酶活性和c-Jun与ICAM-1启动子上的AP-1元件的结合。综上所述，我们的结果表明，CCN 6通过增加ICAM-1的表达，通过α v β 3和α v β 5整合素受体，FAK，MEK，ERK，c-Jun和AP-1信号转导途径，增强软骨肉瘤细胞的迁移。J.细胞。227：223-232，2012。(C)2011 Wiley Periodicals，Inc.
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN6 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, and Nov) family of matricellular proteins. However, the effects of CCN6 on human chondrosarcoma cells are largely unknown. In this study, we found that CCN6 increased the migration and the expression of intercellular adhesion molecule-1 (ICAM-1) in human chondrosarcoma cells. alpha v beta 3 and alpha v beta 5 integrin monoclonal antibody and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) inhibited the CCN6-induced increase of the migration and ICAM-1 up-regulation of chondrosarcoma cells. CCN6 stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK, and extracellular signal-regulated kinase (ERK). In addition, activator protein-1 (AP-1) inhibitors suppressed the cell migration and ICAM-1 expression enhanced by CCN6. Moreover, CCN6 increased AP-1 luciferase activity and binding of c-Jun to the AP-1 element on the ICAM-1 promoter. Taken together, our results indicate that CCN6 enhances the migration of chondrosarcoma cells by increasing ICAM-1 expression through the alpha v beta 3 and alpha v beta 5 integrin receptor, FAK, MEK, ERK, c-Jun, and AP-1 signal transduction pathway. J. Cell. Physiol. 227: 223-232, 2012. (C) 2011 Wiley Periodicals, Inc.