Hybrids by tumor-associated macrophages × glioblastoma cells entail nuclear reprogramming and glioblastoma invasion. (1st February 2019)

• Record Type: Journal Article
• Authors: Cao, Mian-Fu; Chen, Lu; Dang, Wei-Qi; Zhang, Xian-Chao; Zhang, Xiang; Shi, Yu; Yao, Xiao-Hong; Li, Qian; Zhu, Jiang; Lin, Yong; Liu, Sha; Chen, Qian; Cui, Yong-Hong; Zhang, Xia; Bian, Xiu-Wu
• Is Part Of: Cancer letters. Volume 442(2019)
• Page Start: 445
• Page End: 452
• Publication Date: 2019-02-01
• Subjects: Tumor microenvironment -- Tumor immunity -- Glioblastoma invasiveness; BMDMs-GFP green fluorescent protein-labeled bone marrow-derived macrophages -- DAPI 4, 6-diamidino-2-phenylindole -- EdU 5-ethynyl-2′-deoxyuridine -- FACS fluorescence-activated cell sorter -- FCM flow cytometry -- FISH fluorescence in situ hybridization -- GBM glioblastoma -- GL261-RFP red fluorescent protein-labeled murine glioblastoma cell line GL261 -- GSEA gene set enrichment analysis -- IDH isocitrate dehydrogenase -- IDH1R132H isocitrate dehydrogenase 1 with R132H mutation -- PDGFRA platelet derived growth factor receptor alpha -- TAMs tumor-associated macrophages; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.11.016
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Hybrid formation is a fundamental process in normal development and tissue homeostasis, while the presence and the biological role of hybrids between tumor-associated macrophages (TAMs) and glioblastoma (GBM) cells remain elusive. In this study, we observed that TAM-GBM cell hybrids existed in human GBM specimens as demonstrated by co-expression of glioma biomarkers (GFAP, IDH1 R132H and PDGFRA) and macrophage biomarkers (CD68 and CD14). Furthermore, TAM-GBM cell hybrids could also be found in C57BL/6 mice orthotopically inoculated with mouse GBM cells labeled with RFP and after co-culture of bone marrow-derived macrophages from GFP-expressed mice with RFP-labeled GBM cells. The hybrids underwent nuclear reprogramming with unique gene expression profile as compared to parental cells. Moreover, glioma invasion-associated genes were enriched in the hybrids that possessed higher invasiveness, and more hybrids in the invasive margin of GBM were observed as compared to GBM core area. Our data demonstrate the presence of TAM-GBM cell hybrids that enhance GBM invasion. With a better understanding of TAM-GBM cell hybrids, new therapeutic strategies targeting GBM will be developed to treat GBM patients. Graphical abstract: Highlights: Hybrids formed by TAMs and tumor cells exist in GBM. TAM-GBM cell hybrids bear nuclear reprogramming with unique gene expression profile. TAM-GBM cell hybrids contribute to GBM invasion.