Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
Biochem Pharmacol. 2012 Feb 1;83(3):335-44. doi: 10.1016/j.bcp.2011.11.013. Epub 2011 Nov 25.
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. Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of cancers. However, the effect of CCL2 on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that CCL2 increased the migration and expression of matrix metalloproteinase (MMP)-9 in human chondrosarcoma cells. CCL2-mediated migration and MMP-9 up-regulation were attenuated by CCR2, Ras, Raf-1, and MEK inhibitor. Activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathway after CCL2 treatment was demonstrated, and CCL2-induced expression of MMP-9 and migration activity were inhibited by the specific inhibitor, and mutant of Ras, Raf-1, MEK, ERK, and NF-κB cascades. Taken together, our results indicated that CCL2 enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the CCR2 receptor, Ras, Raf-1, MEK, ERK, and NF-κB signal transduction pathway.
软骨肉瘤是一种高度恶性肿瘤，具有很强的局部侵袭和远处转移能力。软骨肉瘤易向肺部转移。趋化因子配体 2（CCL2），也称为单核细胞趋化蛋白-1（MCP-1），属于 CC 趋化因子家族，与癌症的疾病状态和预后有关。然而，CCL2 对人软骨肉瘤细胞迁移活性的影响大多未知。在这里，我们发现 CCL2 增加了人软骨肉瘤细胞的迁移和基质金属蛋白酶（MMP）-9 的表达。CCL2 介导的迁移和 MMP-9 的上调被 CCR2、Ras、Raf-1 和 MEK 抑制剂减弱。证明 CCL2 处理后 Ras、Raf-1、MEK、ERK 和 NF-κB 信号通路被激活，CCL2 诱导的 MMP-9 表达和迁移活性被特定抑制剂和 Ras、Raf-1、MEK、ERK 和 NF-κB 信号转导途径的突变体抑制。综上所述，我们的研究结果表明，CCL2 通过 CCR2 受体、Ras、Raf-1、MEK、ERK 和 NF-κB 信号转导途径增加 MMP-9 的表达，增强软骨肉瘤细胞的迁移。
