Li Yueguo, Wu Jing, Zhang Peng
Department of Clinical Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
Key Laboratory of Cancer Prevention and Therapy, The National "863" Program of Clinical Research Laboratory, Tianjin, 300060, People's Republic of China.
Tumour Biol. 2016 Apr;37(4):4501-7. doi: 10.1007/s13277-015-4287-0. Epub 2015 Oct 26.
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.
鉴定用于早期检测肝细胞癌的新生物标志物对于肿瘤靶向治疗的发展至关重要，这可能对该疾病的预后具有优势。我们先前研究的结果表明，CCL15可能是肝细胞癌的一种特异性蛋白质组学生物标志物，其在肿瘤发生和肿瘤侵袭中起重要作用。在本研究中，我们发现CCL15可诱导肝癌细胞迁移和侵袭。此外，CCL15的受体CCR1在转移性肝细胞癌中起关键作用。CCR1短发夹RNA显著抑制CCL15诱导的HepG2细胞趋化性和侵袭。此外，CCR1基因敲低显著限制了基质金属蛋白酶-2（MMP-2）和MMP-9的活性及表达。这些发现表明CCR1在肝细胞癌转移中起关键作用，这表明CCR1可能是肝细胞癌治疗中的潜在分子靶点。
