CXCL12-CXCR4/CXCR7轴在胃癌中作用的研究进展  

Research progress in the role of CXCL12-CXCR4/CXCR7 axis in gastric cancer

作　　者：袁思敏 李亚玲 李长天 YUAN Simin;LI Yaling;LI Changtian(First School of Clinical Medicine,Gansu University of Chinese Medicine,Lanzhou 730000;School of Basic Medical Sciences,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学第一临床医学院,兰州730000 [2]甘肃中医药大学基础医学院,兰州730000

出　　处：《临床与病理杂志》2023年第9期1683-1689,共7页Journal of Clinical and Pathological Research

摘　　要：胃癌(gastric cancer,GC)是最常见的消化系统恶性肿瘤,发病率高,预后差。趋化因子配体12(chemokine ligand 12,CXCL12)-趋化因子受体(chemokine receptor,CXCR)4/CXCR7轴及其下游的信号通路参与了GC的发生、发展过程。CXCL12结合CXCR4时,可通过诱导上皮-间充质转化(epithelial-mesenchymal transition,EMT)而调节血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,激活不同的信号通路[如磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)、Wnt信号通路和核因子-kappa B(nuclear factor-kappa B,NF-κB)等]机制,促进GC的增殖、侵袭和转移。当CXCL12与CXCR7结合时,可增加GC细胞中基质金属蛋白酶(matrix metalloproteinase,MMP)-2和MMP-9的表达,从而促进GC细胞的迁移和侵袭能力;还可以通过调节Akt、信号转导和转录激活因子3/骨髓瘤病毒癌基因同源物(signal transduer and activator of transcription 3/myelocytomatosis viral oncogene homolog,STAT3/c-Myc)信号通路加快GC进展。此外,CXCL12-CXCR4/CXCR7轴与GC的肿瘤免疫密切相关,能介导T细胞、B细胞、NK细胞、巨噬细胞以及中性粒细胞等免疫细胞的发展,可为GC的免疫治疗提供新思路。Gastric cancer(GC)is the most common malignant tumor in the digestive system,characterized by high incidence and poor prognosis.The chemokine ligand 12(CXCL12)-chemokine receptor(CXCR)4/CXCR7 axis and its downstream signaling pathways are involved in the initiation and progression of gastric cancer.When CXCL12 binds to CXCR4,it regulates the expression of vascular endothelial growth factor(VEGF)by inducing epithelial-mesenchymal transition(EMT),activates various signaling pathways,such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),Wnt signaling pathway,and nuclear factor-kappa B(NF-κB)and other mechanisms,and enhances proliferation,invasion,and metastasis in GC.Coversely,CXCL12 binding to CXCR7 increases the expression of matrix metalloproteinases(MMP)-2 and MMP-9 in GC cells,thus promoting their migration and invasion capabilities.Furthermore,the CXCL12-CXCR4/CXCR7 axis accelerates GC progression by regulating protein kinase B(Akt),signal transducer and activator of transcription 3/myelocytomatosis viral oncogene homolog(STAT3/c-Myc)signaling pathways.Additionally,this axis is closely related to tumor immune response in GC and mediates the development of immune cells,such as T cells,B cells,NK cells,macrophages,and neutrophils,suggesting new prospects for GC immunotherapy.

关 键 词：胃癌 趋化因子配体12 趋化因子受体4 趋化因子受体7 

分 类 号：R735.2[医药卫生—肿瘤]