title: Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages.
abstract: Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.
authors.affiliation: Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Ian
authors.initials: I
authors.lastname: Zhang
authors.affiliation: Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Darya
authors.initials: D
authors.lastname: Alizadeh
authors.affiliation: Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liang
authors.affiliation: Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Leying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Bone and Joint Surgery, No.1 Hospital of Jilin University, Changchun, Jilin Province, P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin Province, P. R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of General Surgery, The Second Hospital of Jilin University, Changchun, Jilin Province, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha Hunan, P. R. China.
authors.forename: Mao
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: Department of Molecular and Cellular Biology, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Apuzzo
authors.affiliation: Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, United States of America.
authors.forename: Behnam
authors.initials: B
authors.lastname: Badie
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D001119:Arginase / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D061251:Primary Cell Culture; D015398:Signal Transduction; D013997:Time Factors; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D000950:Antigens, Ly; C480309:Ly6G antigen, mouse; D009363:Neoplasm Proteins; C544448:Arg1 protein, mouse; D001119:Arginase