1. Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages.
- Author
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Zhang I, Alizadeh D, Liang J, Zhang L, Gao H, Song Y, Ren H, Ouyang M, Wu X, D'Apuzzo M, and Badie B
- Subjects
- Animals, Antigens, Ly genetics, Antigens, Ly metabolism, Arginase metabolism, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cell Line, Tumor, Female, Gene Expression Profiling, Glioma metabolism, Glioma pathology, Humans, Macrophage Activation, Macrophages pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia pathology, Neoplasm Proteins metabolism, Neoplasm Transplantation, Organ Specificity, Primary Cell Culture, Signal Transduction, Time Factors, Tumor Microenvironment genetics, Arginase genetics, Brain Neoplasms genetics, Gene Expression Regulation, Neoplastic, Glioma genetics, Macrophages metabolism, Microglia metabolism, Neoplasm Proteins genetics
- 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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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