C.-Y. Chuang, W.-H. Yang, and H.-T. Chen contributed equally to this study.
CCL5/CCR5 axis promotes the motility of human oral cancer cells†
Article first published online: 30 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 220, Issue 2, pages 418–426, August 2009
How to Cite
Chuang, J.-Y., Yang, W.-H., Chen, H.-T., Huang, C.-Y., Tan, T.-W., Lin, Y.-T., Hsu, C.-J., Fong, Y.-C. and Tang, C.-H. (2009), CCL5/CCR5 axis promotes the motility of human oral cancer cells. J. Cell. Physiol., 220: 418–426. doi: 10.1002/jcp.21783
- Issue published online: 26 MAY 2009
- Article first published online: 30 MAR 2009
- Manuscript Accepted: 3 MAR 2009
- Manuscript Received: 19 NOV 2008
- National Science Council of Taiwan. Grant Numbers: NSC96-2320-B-039-028-MY3, NSC97-2320-B-039-031-MY3, NSC97-2314-B-039-032-MY2
- China Medical University. Grant Numbers: CMU97-106, 97-092
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 Cδ (PKCδ), and NF-κB pathways after CCL5 treatment was demonstrated, and CCL5-induced expression of MMP-9 and migration activity was inhibited by the specific inhibitor of PLC, PKCδ, and NF-κB 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. J. Cell. Physiol. 220: 418–426, 2009. © 2009 Wiley-Liss, Inc.