Ding Qiang, Xia Yujia, Ding Shuping, Lu Panpan, Sun Liang, Liu Mei
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Oncotarget. 2016 Mar 22;7(12):14405-14. doi: 10.18632/oncotarget.7360.
Metastasis of liver cancer is closely linked to tumor microenvironment, in which chemokines and their receptors act in an important role. The CXCR3, the receptor of chemokine CXCL9, belongs to a superfamily of rhodopsin-like seven transmembrane GPCRs and CXCR subfamily. In HCC tissues, CXCR3 was frequently upregulated and correlated with tumor size, tumor differentiation, portal invasion and metastasis. In the study, CXCR3-A isoform that was bound by CXCL9 was found to cause significant change of ERK1/2 phosphorylation level in the MAPK signaling pathway, consequently upregulating the MMP2 and MMP9 expression and promoting invasion and metastasis of CD133+ liver cancer cells. Also, CXCR3-A suppressed the adhesion ability of CD133+ liver cancer cells that stimulated by CXCL9 for 24h. These findings suggest that CXCR3 and its ligand CXCL9 could promote the metastasis of liver cancer cells and might be a potential target for the intervention of liver cancer metastasis.
肝癌转移与肿瘤微环境密切相关，其中趋化因子及其受体发挥着重要作用。趋化因子CXCL9的受体CXCR3属于视紫红质样七跨膜GPCR超家族和CXCR亚家族。在肝癌组织中，CXCR3经常上调，并与肿瘤大小、肿瘤分化、门静脉侵犯和转移相关。在该研究中，发现与CXCL9结合的CXCR3-A亚型可导致MAPK信号通路中ERK1/2磷酸化水平发生显著变化，从而上调MMP2和MMP9的表达，并促进CD133+肝癌细胞的侵袭和转移。此外，CXCR3-A抑制了CXCL9刺激24小时的CD133+肝癌细胞的黏附能力。这些发现表明，CXCR3及其配体CXCL9可促进肝癌细胞的转移，可能是干预肝癌转移的潜在靶点。
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