Ren Tingting, Zhu Lili, Cheng Mingliang
Department of Biochemistry, Affiliated Hospital of Guiyang Medical College28 Guiyi Street, Guiyang 550004, Guizhou, China.
The Affiliated Baiyun Hospital of Guizhou Medical UniversityGuiyang 550004, Guizhou, China.
Am J Transl Res. 2017 Jun 15;9(6):2824-2837. eCollection 2017.
Human malignant hepatocellular carcinoma (HCC) is a common tumor, which severely threatens human health and shortens longevity. The poor prognosis of HCC is primarily attributed to distant metastases. C-X-C motif chemokine 10 (CXCL10) regulates the control of several cellular and developmental processes including tumor cell proliferation, apoptosis, and cell metastasis. Previous studies have confirmed that CXCL10 functions as an oncogene in several cancers. However, the expression and biological functions of CXCL10 in HCC, especially with regard to metastasis, need further investigation. In this study, CXCL10 was found to be over expressed in invasive HCC cells and HCC clinical samples. While the over-expression of CXCL10 enhanced migration, invasion, and metastasis of HCC cells in vitro as well as in vivo, silencing of CXCL10 resulted in inhibition of HCC cell metastasis. Further, CXCL10 was found to accelerate epithelial-mesenchymal transition of HCC cells. The microarray analysis indicated that matrix metallopeptidase-2 (MMP-2) functions as a downstream factor of CXCL10. This study demonstrates that CXCL10 partakes in the metastasis of HCC by activating MMP-2 expression.
人类恶性肝细胞癌（HCC）是一种常见肿瘤，严重威胁人类健康并缩短寿命。HCC预后不良主要归因于远处转移。C-X-C基序趋化因子10（CXCL10）调控多种细胞和发育过程，包括肿瘤细胞增殖、凋亡及细胞转移。既往研究证实CXCL10在多种癌症中作为癌基因发挥作用。然而，CXCL10在HCC中的表达及生物学功能，尤其是与转移相关的功能，仍需进一步研究。本研究发现CXCL10在侵袭性HCC细胞和HCC临床样本中过表达。CXCL10的过表达增强了HCC细胞在体外及体内的迁移、侵袭和转移能力，而CXCL10沉默则导致HCC细胞转移受到抑制。此外，还发现CXCL10可加速HCC细胞的上皮-间质转化。微阵列分析表明基质金属蛋白酶-2（MMP-2）作为CXCL10的下游因子发挥作用。本研究证明CXCL10通过激活MMP-2表达参与HCC的转移。
