title: Subsets of myeloid-derived suppressor cells in hepatocellular carcinoma express chemokines and chemokine receptors differentially.
abstract: Tumors induce the recruitment and expansion of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells that can be further sub-divided into polymorphonuclear Ly6G(+) PMN-MDSCs and monocytic Ly6G(-) Mo-MDSCs. To identify chemokines and chemokine-related genes that are differentially expressed within the tumor microenvironment in these two MDSC subsets, we established an orthotopic hepatocellular carcinoma model in immunocompetent mice. Splenic PMN-MDSCs and Mo-MDSCs were isolated to >95% homogeneity by flow cytometry. Using a real-time PCR array, we investigated the expression of 84 genes encoding chemokines and cytokines, chemokine receptors, and related signaling molecules involved with chemotaxis. Clustering analysis suggested that a core set of chemokine-related genes is expressed in both PMN-MDSC and Mo-MDSC populations, but that the expression profile is broader for Mo-MDSCs. Furthermore, 11 genes are more highly expressed in PMN-MDSCs and 12 genes are more highly expressed in Mo-MDSCs. Among these, PMN-MDSCs express Cxcr1, Cxcr2 and Il1b at 33.03- to 109.76-fold higher levels than in Mo-MDSCs, and Mo-MDSCs express eight genes (Ccr2, Ccr5, Cmklr1, Cx3cr1, Ccr3, Ccl9, Cmtm3 and Cxcl16) at 30.2 to 515.5-fold higher levels than in PMN-MDSCs. These results suggest that the profile of chemokines and chemokine-related genes is more expansive for Mo-MDSCs than for PMN-MDSCs. The differential expression of chemokines and chemokine-associated genes may regulate the presence and activity of PMN-MDSCs and Mo-MDSCs in the tumor microenvironment.
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China.
authors.forename: Bixing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China. Electronic address: yinzy@xmu.edu.cn.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, China. Electronic address: wxm2203@xmu.edu.cn.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007108:Immune Tolerance; D008113:Liver Neoplasms / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: C515335:Ccr2 protein, mouse; D018925:Chemokines; D054390:Receptors, CCR2; D023062:Receptors, Interleukin-8A
keywords: Chemokine receptors; Chemokines; Hepatocellular carcinoma; Myeloid-derived suppressor cells