Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis
Abstract Background Exosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropis...
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1149-5 |
| _version_ | 1828962488379506688 |
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| author | Zhanjun Ma Xue Cui Li Lu Guohu Chen Yang Yang Yan Hu Yubao Lu Zhangqi Cao Yan Wang Xuexi Wang |
| author_facet | Zhanjun Ma Xue Cui Li Lu Guohu Chen Yang Yang Yan Hu Yubao Lu Zhangqi Cao Yan Wang Xuexi Wang |
| author_sort | Zhanjun Ma |
| collection | DOAJ |
| description | Abstract Background Exosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have been used as tumor-tropic vectors for tumor therapy; however, the safety of such therapeutic use of MSCs is unknown. In this study, we investigated the role of glioma cell-derived exosomes in the tumor-like phenotype transformation of human bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular mechanisms. Methods The effect of exosomes from U251 glioma cells on the growth of hBMSCs was evaluated with the CCK-8 assay, KI67 staining, and a cell cycle distribution assessment. The migration and invasion of hBMSCs were evaluated with a Transwell assay. A proteomics and bioinformatics approach, together with Western blotting and reverse transcriptase-polymerase chain reaction, was used to investigate the effect of U251 cell-derived exosomes on the proteome of hBMSCs. Results U251 cell-derived exosomes induced a tumor-like phenotype in hBMSCs by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle. Moreover, U251 cell-derived exosomes promoted the production of the metastasis-related proteins MMP-2 and MMP-9, glioma marker GFAP, and CSC markers (CD133 and Nestin). The ten differentially expressed proteins identified participated in several biological processes and exhibited various molecular functions, mainly related to the inactivation of glycolysis. Western blotting showed that U251 cell-derived exosomes upregulated the levels of Glut-1, HK-2, and PKM-2, leading to the induction of glucose consumption and generation of lactate and ATP. Treatment with 2-deoxy-d-glucose significantly reversed these effects of U251 cell-derived exosomes on hBMSCs. Conclusions Our data demonstrate that glioma cell-derived exosomes activate glycolysis in hBMSCs, resulting in their tumor-like phenotype transformation. This suggests that interfering with the interaction between exosomes and hBMSCs in the tumor microenvironment has potential as a therapeutic approach for glioma. Graphical abstract ᅟ |
| first_indexed | 2024-12-14T10:05:01Z |
| format | Article |
| id | doaj.art-01582213e6984f9a997bd97d27be425c |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-14T10:05:01Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-01582213e6984f9a997bd97d27be425c2022-12-21T23:07:09ZengBMCStem Cell Research & Therapy1757-65122019-02-0110111810.1186/s13287-019-1149-5Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysisZhanjun Ma0Xue Cui1Li Lu2Guohu Chen3Yang Yang4Yan Hu5Yubao Lu6Zhangqi Cao7Yan Wang8Xuexi Wang9The Second Clinical Medical College, Lanzhou UniversityThe First Clinical Medical College, Lanzhou UniversityInstitute of Pharmacology, School of Basic Medical Science, Lanzhou UniversityThe First Clinical Medical College, Lanzhou UniversityThe Second Clinical Medical College, Lanzhou UniversitySchool of Basic Medical Sciences, Lanzhou UniversityThe Second Clinical Medical College, Lanzhou UniversitySchool of Basic Medical Sciences, Lanzhou UniversitySchool of Basic Medical Sciences, Lanzhou UniversitySchool of Basic Medical Sciences, Lanzhou UniversityAbstract Background Exosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have been used as tumor-tropic vectors for tumor therapy; however, the safety of such therapeutic use of MSCs is unknown. In this study, we investigated the role of glioma cell-derived exosomes in the tumor-like phenotype transformation of human bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular mechanisms. Methods The effect of exosomes from U251 glioma cells on the growth of hBMSCs was evaluated with the CCK-8 assay, KI67 staining, and a cell cycle distribution assessment. The migration and invasion of hBMSCs were evaluated with a Transwell assay. A proteomics and bioinformatics approach, together with Western blotting and reverse transcriptase-polymerase chain reaction, was used to investigate the effect of U251 cell-derived exosomes on the proteome of hBMSCs. Results U251 cell-derived exosomes induced a tumor-like phenotype in hBMSCs by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle. Moreover, U251 cell-derived exosomes promoted the production of the metastasis-related proteins MMP-2 and MMP-9, glioma marker GFAP, and CSC markers (CD133 and Nestin). The ten differentially expressed proteins identified participated in several biological processes and exhibited various molecular functions, mainly related to the inactivation of glycolysis. Western blotting showed that U251 cell-derived exosomes upregulated the levels of Glut-1, HK-2, and PKM-2, leading to the induction of glucose consumption and generation of lactate and ATP. Treatment with 2-deoxy-d-glucose significantly reversed these effects of U251 cell-derived exosomes on hBMSCs. Conclusions Our data demonstrate that glioma cell-derived exosomes activate glycolysis in hBMSCs, resulting in their tumor-like phenotype transformation. This suggests that interfering with the interaction between exosomes and hBMSCs in the tumor microenvironment has potential as a therapeutic approach for glioma. Graphical abstract ᅟhttp://link.springer.com/article/10.1186/s13287-019-1149-5ExosomesGlioma cellsGlycolytic pathwayTumor-like phenotype transformationMesenchymal stem cellsProteomics |
| spellingShingle | Zhanjun Ma Xue Cui Li Lu Guohu Chen Yang Yang Yan Hu Yubao Lu Zhangqi Cao Yan Wang Xuexi Wang Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis Stem Cell Research & Therapy Exosomes Glioma cells Glycolytic pathway Tumor-like phenotype transformation Mesenchymal stem cells Proteomics |
| title | Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis |
| title_full | Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis |
| title_fullStr | Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis |
| title_full_unstemmed | Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis |
| title_short | Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis |
| title_sort | exosomes from glioma cells induce a tumor like phenotype in mesenchymal stem cells by activating glycolysis |
| topic | Exosomes Glioma cells Glycolytic pathway Tumor-like phenotype transformation Mesenchymal stem cells Proteomics |
| url | http://link.springer.com/article/10.1186/s13287-019-1149-5 |
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