骨肉瘤是最常見的惡性,、原發(fā)性骨腫瘤,，其惡性程度高,、發(fā)展迅速,，如未經正規(guī)治療，半年至一年內腫瘤就會發(fā)生肺轉移,，導致患者死亡,。
CCL5曾被稱為RANTES，最初被發(fā)現(xiàn)是激活的T細胞的產物,，并對人類癌細胞的轉移起著重要作用,。
已知CCR受體調節(jié)了CCL5的功能，然而在人類骨肉瘤細胞中CCL5對遷移能力及整合素的表達的功能還不可知,。
最近臺灣中國醫(yī)藥大學的研究人員發(fā)現(xiàn),，人類骨肉瘤細胞的CCL5促進了αvβ3整合素的遷移及表達。而且,，刺激CCL5細胞會提升CCR5而不是CCR5及CCR3的表達,。
在骨肉瘤細胞里，CCR5 mAb,、抑制劑及siRNA降低了CCL5促進的遷移能力及整合素的上調作用,。
實驗發(fā)現(xiàn)，經過CCL5的處理后,，激活了MEK,、ERK及NF-κB通路。CCL5誘導的整合素表達及遷移活性通過特定的抑制劑被抑制,。
除此以外,，在骨肉瘤細胞CCL5 shRNA的過表達抑制了遷移能力及整合素的表達。
結果表明,，通過MEK和ERK,，CCL5與CCR5相互作用,，反過來激活了NF-κB,，導致了αvβ3整合素的激活,，促進了人類骨肉瘤細胞的遷移。相關論文發(fā)表在4月10日的Plos One,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0035101
PMC:
PMID:
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.
