Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis
Abstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03607-0 |
| _version_ | 1817994133104492544 |
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| author | Chunzhi Zhang Yuan Zhou Ya Gao Ze Zhu Xianliang Zeng Weizi Liang Songwei Sun Xiuli Chen Hu Wang |
| author_facet | Chunzhi Zhang Yuan Zhou Ya Gao Ze Zhu Xianliang Zeng Weizi Liang Songwei Sun Xiuli Chen Hu Wang |
| author_sort | Chunzhi Zhang |
| collection | DOAJ |
| description | Abstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate of irradiated glioblastoma cells remains to be elucidated. Methods We erected the co-culture system of glioblastoma cells and microglia. After radiation, we analyzing the immunophenotype of microglia and the proliferation of radiated glioblastoma cells. By whole transcriptome sequencing, we analyzed of circRNAs in exosomes from glioblastoma cells and microglia. We used some methods, which included RT-PCR, dual-luciferase reporter, et al., to identify how circ_0012381 from radiated glioblastoma cell-derived exosomes regulated the immunophenotype of microglia to further affect the proliferation of radiated glioblastoma cells. Results Radiated glioblastoma cell-derived exosomes markedly induced M2 microglia polarization. These M2-polarized microglia promoted the proliferation of irradiated glioblastoma cells. Circ_0012381 expression was increased in the irradiated glioblastoma cells, and circ_0012381 entered the microglia via exosomes. Circ_0012381 induced M2 microglia polarization by sponging with miR-340-5p to increase ARG1 expression. M2-polarized microglia suppressed phagocytosis and promoted the growth of the irradiated glioblastoma cells by CCL2/CCR2 axis. Compared with the effects of radiotherapy alone, the inhibition of exosomes significantly inhibited the growth of irradiated glioblastoma cells in a zebrafish model. Conclusions Our data suggested that the inhibition of exosome secretion might represent a potential therapeutic strategy to increase the efficacy of radiotherapy in patients with glioblastoma. |
| first_indexed | 2024-04-14T01:47:49Z |
| format | Article |
| id | doaj.art-943dad18d0e54eeca5ebb58d66ae770e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-14T01:47:49Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-943dad18d0e54eeca5ebb58d66ae770e2022-12-22T02:19:27ZengBMCJournal of Translational Medicine1479-58762022-09-0120111310.1186/s12967-022-03607-0Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axisChunzhi Zhang0Yuan Zhou1Ya Gao2Ze Zhu3Xianliang Zeng4Weizi Liang5Songwei Sun6Xiuli Chen7Hu Wang8Department of Radiation Oncology, Tianjin HospitalTianjin Medical UniversityDepartment of Pathogenic Biology, Basic Medical College, Tianjin Medical UniversityDepartment of Pathogenic Biology, Basic Medical College, Tianjin Medical UniversityDepartment of Radiation Oncology, Tianjin HospitalDepartment of Radiation Oncology, Tianjin HospitalDepartment of Radiation Oncology, Tianjin HospitalDepartment of Radiation Oncology, Tianjin HospitalDepartment of Neuro-Surgery, Tianjin Huanhu HospitalAbstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate of irradiated glioblastoma cells remains to be elucidated. Methods We erected the co-culture system of glioblastoma cells and microglia. After radiation, we analyzing the immunophenotype of microglia and the proliferation of radiated glioblastoma cells. By whole transcriptome sequencing, we analyzed of circRNAs in exosomes from glioblastoma cells and microglia. We used some methods, which included RT-PCR, dual-luciferase reporter, et al., to identify how circ_0012381 from radiated glioblastoma cell-derived exosomes regulated the immunophenotype of microglia to further affect the proliferation of radiated glioblastoma cells. Results Radiated glioblastoma cell-derived exosomes markedly induced M2 microglia polarization. These M2-polarized microglia promoted the proliferation of irradiated glioblastoma cells. Circ_0012381 expression was increased in the irradiated glioblastoma cells, and circ_0012381 entered the microglia via exosomes. Circ_0012381 induced M2 microglia polarization by sponging with miR-340-5p to increase ARG1 expression. M2-polarized microglia suppressed phagocytosis and promoted the growth of the irradiated glioblastoma cells by CCL2/CCR2 axis. Compared with the effects of radiotherapy alone, the inhibition of exosomes significantly inhibited the growth of irradiated glioblastoma cells in a zebrafish model. Conclusions Our data suggested that the inhibition of exosome secretion might represent a potential therapeutic strategy to increase the efficacy of radiotherapy in patients with glioblastoma.https://doi.org/10.1186/s12967-022-03607-0GlioblastomaRadiotherapyExosomeMicrogliaM2 |
| spellingShingle | Chunzhi Zhang Yuan Zhou Ya Gao Ze Zhu Xianliang Zeng Weizi Liang Songwei Sun Xiuli Chen Hu Wang Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis Journal of Translational Medicine Glioblastoma Radiotherapy Exosome Microglia M2 |
| title | Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis |
| title_full | Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis |
| title_fullStr | Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis |
| title_full_unstemmed | Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis |
| title_short | Radiated glioblastoma cell-derived exosomal circ_0012381 induce M2 polarization of microglia to promote the growth of glioblastoma by CCL2/CCR2 axis |
| title_sort | radiated glioblastoma cell derived exosomal circ 0012381 induce m2 polarization of microglia to promote the growth of glioblastoma by ccl2 ccr2 axis |
| topic | Glioblastoma Radiotherapy Exosome Microglia M2 |
| url | https://doi.org/10.1186/s12967-022-03607-0 |
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