CCL15/CCR1 axis is involved in hepatocellular carcinoma cells migration and invasion.

The identification of new biomarkers for the early detection of hepatocellular carcinoma is critical in the development of tumor-targeted therapy, which is possibly advantageous on the prognosis of this disease. Results from our previous study indicated that CCL15 can be a specific proteomic biomarker of hepatocellular carcinoma, which plays an important role in tumorigenesis and tumor invasion. In this study, we found that CCL15 can induce hepatocellular carcinoma cell migration and invasion. Furthermore, CCR1, the receptor of CCL15, was demonstrated to play a critical role in metastatic hepatocellular carcinoma. CCR1 short hairpin RNA significantly inhibited CCL15-induced chemotaxis and invasion of HepG2 cells. Moreover, CCR1 knockdown significantly limited the activity and expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. These findings suggest that CCR1 plays critical roles in hepatocellular carcinoma metastasis, which indicates that CCR1 may be a potential molecular target in hepatocellular carcinoma therapy.