Plos One：发现人类骨肉瘤细胞迁移的促进机制

骨肉瘤是最常见的恶性、原发性骨肿瘤，其恶性程度高、发展迅速，如未经正规治疗，半年至一年内肿瘤就会发生肺转移，导致患者死亡。

CCL5曾被称为RANTES，最初被发现是激活的T细胞的产物，并对人类癌细胞的转移起着重要作用。

已知CCR受体调节了CCL5的功能，然而在人类骨肉瘤细胞中CCL5对迁移能力及整合素的表达的功能还不可知。

最近台湾中国医药大学的研究人员发现，人类骨肉瘤细胞的CCL5促进了αvβ3整合素的迁移及表达。而且，刺激CCL5细胞会提升CCR5而不是CCR5及CCR3的表达。

在骨肉瘤细胞里，CCR5 mAb、抑制剂及siRNA降低了CCL5促进的迁移能力及整合素的上调作用。

实验发现，经过CCL5的处理后，激活了MEK、ERK及NF-κB通路。CCL5诱导的整合素表达及迁移活性通过特定的抑制剂被抑制。

除此以外，在骨肉瘤细胞CCL5 shRNA的过表达抑制了迁移能力及整合素的表达。

结果表明，通过MEK和ERK，CCL5与CCR5相互作用，反过来激活了NF-κB，导致了αvβ3整合素的激活，促进了人类骨肉瘤细胞的迁移。相关论文发表在4月10日的Plos One。（生物谷Deepblue编译）

doi: 10.1371/journal.pone.0035101
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CCL5 and CCR5 Interaction Promotes Cell Motility in Human Osteosarcoma

Shih-Wei Wang, Hsing-Hsien Wu, Shih-Chia Liu, Po-Chuan Wang, Wen-Chieh Ou, Wen-Yi Chou, Yung-Shuen Shen,Chih-Hsin Tang.

Osteosarcoma is characterized by a high malignant and metastatic potential.CCL5 (previously called RANTES) was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells.It has been reported that the effect of CCL5 is mediated via CCR receptors.However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown.Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression.CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells.Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades.In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells.CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.