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, IDH1R132H 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.
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Authors | Mian-Fu Cao, Lu Chen, Wei-Qi Dang, Xian-Chao Zhang, Xiang Zhang, Yu Shi, Xiao-Hong Yao, Qian Li, Jiang Zhu, Yong Lin, Sha Liu, Qian Chen, Yong-Hong Cui, Xia Zhang, Xiu-Wu Bian |
Journal | Cancer letters
(Cancer Lett)
Vol. 442
Pg. 445-452
(02 01 2019)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 30472185
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Topics |
- Animals
- Brain Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Movement
- Cellular Reprogramming
- Coculture Techniques
- Female
- Gene Expression Regulation, Neoplastic
- Glioblastoma
(genetics, metabolism, secondary)
- Humans
- Hybrid Cells
(metabolism, pathology)
- Macrophages
(metabolism, pathology)
- Mice, Inbred C57BL
- Mice, Transgenic
- Neoplasm Invasiveness
- Phenotype
- Transcriptome
- Tumor Microenvironment
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