Chuang Jing-Yuan, Yang Wei-Hung, Chen Hsien-Te, Huang Chun-Yin, Tan Tzu-Wei, Lin Yuh-Tzy, Hsu Chin-Jung, Fong Yi-Chin, Tang Chih-Hsin
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung Taiwan.
J Cell Physiol. 2009 Aug;220(2):418-26. doi: 10.1002/jcp.21783.
CCL5 (previously called RANTES) is in the CC-chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT-PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase-9 (MMP-9) production. MMP-9 small interfering RNA inhibited the CCL5-induced MMP-9 expression and thereby significantly inhibited the CCL5-induced cell migration. Activations of phospholipase C (PLC), protein kinase Cdelta (PKCdelta), and NF-kappaB pathways after CCL5 treatment was demonstrated, and CCL5-induced expression of MMP-9 and migration activity was inhibited by the specific inhibitor of PLC, PKCdelta, and NF-kappaB cascades. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP-9 production.
CCL5（以前称为RANTES）属于CC趋化因子家族，在人类癌细胞的迁移和转移中起关键作用。另一方面，CCL5的作用是通过CCR受体介导的。逆转录聚合酶链反应（RT-PCR）和流式细胞术研究表明，口腔癌细胞系中存在CCR5 mRNA，但不存在CCR1和CCR3 mRNA，尤其是侵袭性高的细胞系（SCC4）中CCR5 mRNA水平较高，而HSC3细胞和SCC9细胞中水平较低。用CCL5刺激口腔癌细胞可直接增加其迁移和金属蛋白酶-9（MMP-9）的产生。MMP-9小干扰RNA抑制CCL5诱导的MMP-9表达，从而显著抑制CCL5诱导的细胞迁移。实验证明了CCL5处理后磷脂酶C（PLC）、蛋白激酶Cδ（PKCδ）和核因子κB（NF-κB）信号通路的激活，并且PLC、PKCδ和NF-κB信号级联的特异性抑制剂可抑制CCL5诱导的MMP-9表达和迁移活性。此外，易于迁移的亚系表明，迁移能力增强的细胞中MMP-9、CCL5和CCR5的表达更多。综上所述，这些结果表明CCL5/CCR5轴通过增加MMP-9的产生增强了口腔癌细胞的迁移。
