RETRACTED ARTICLE: Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis
2019
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. 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. 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. 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. ᅟ
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