VEGFA contributes to tumor property of glioblastoma cells by promoting differentiation of myeloid-derived suppressor cells.

Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Glioblastoma*/pathology ; Glioblastoma*/metabolism ; Glioblastoma*/genetics ; Cell Differentiation* ; Vascular Endothelial Growth Factor A*/metabolism ; Vascular Endothelial Growth Factor A*/genetics ; Myeloid-Derived Suppressor Cells*/metabolism ; Myeloid-Derived Suppressor Cells*/pathology ; Apoptosis* ; Cell Proliferation* ; Transforming Growth Factor beta1*/metabolism ; Transforming Growth Factor beta1*/genetics; Humans ; Animals ; Mice ; Cell Line, Tumor ; Cell Movement/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/metabolism ; Brain Neoplasms/genetics ; Gene Expression Regulation, Neoplastic ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/pathology ; Xenograft Model Antitumor Assays ; Female

Background: Glioblastoma (GBM) is a malignant astrocytic tumor and its progression involves the regulation of vascular endothelial growth factor-A (VEGFA). However, the mechanism of VEGFA in regulating GBM progression remains unclear.
Methods: VEGFA mRNA expression was analyzed by quantitative real-time polymerase chain reaction. Protein expression of VEGFA, cluster of differentiation 9 (CD9), CD81, and transforming growth factor-β1 (TGF-β1) was detected by western blotting assay. Flow cytometry assay was conducted to assess cell proliferation, cell apoptosis and myeloid-derived suppressor cell (MDSC) differentiation. TUNEL cell apoptosis detection kit was utilized to analyze cell apoptosis of tumors. Angiogenic capacity was investigated by tube formation assay. Transwell assay was used to assess cell migration and invasion. The effect of VEGFA on tumor formation was determined by a xenograft mouse model assay. Immunohistochemistry assay was used to analyze positive expression rate of VEGFA in tumor tissues. TGF-β1 level was detected by enzyme-linked immunosorbent assay.
Results: VEGFA expression was upregulated in GBM tissues, GBM cells, and exosomes from GBM patients and GBM cells. VEGFA silencing led to decreased cell proliferation, tube formation, migration and invasion and increased cell apoptosis. Moreover, VEGFA knockdown also delayed tumor formation. VEGFA promoted MDSC differentiation and TGF-β1 secretion by MDSCs by being packaged into exosomes. In addition, TGF-β1 knockdown displayed similar effects with VEGFA silencing on GBM cell phenotypes, and MDSCs attenuated VEGFA knockdown-induced effects by secreting TGF-β1 in A172 and U251 cells.
Conclusion: VEGFA contributed to tumor property of GBM cells by promoting MDSC differentiation and TGF-β1 secretion by MDSCs, providing potential targets for GBM treatment.
(© 2024. The Author(s).)

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S2022-ZDYF-SF-1283 Xianyang key research and development Project; S2022-ZDYF-SF-1283 Xianyang key research and development Project; S2022-ZDYF-SF-1283 Xianyang key research and development Project; S2022-ZDYF-SF-1283 Xianyang key research and development Project; S2022-ZDYF-SF-1283 Xianyang key research and development Project; 215KYJJ-202209 No. 215 Hospital of Shaanxi Nuclear Industry scientific research project; 215KYJJ-202209 No. 215 Hospital of Shaanxi Nuclear Industry scientific research project; 215KYJJ-202209 No. 215 Hospital of Shaanxi Nuclear Industry scientific research project; 215KYJJ-202209 No. 215 Hospital of Shaanxi Nuclear Industry scientific research project; 215KYJJ-202209 No. 215 Hospital of Shaanxi Nuclear Industry scientific research project

Keywords: Exosomes; GBM; MDSC; TGF-β1; VEGFA

0 (Vascular Endothelial Growth Factor A)
0 (VEGFA protein, human)
0 (Transforming Growth Factor beta1)
0 (TGFB1 protein, human)

Date Created: 20240822 Date Completed: 20240823 Latest Revision: 20240825

20240826

PMC11342494

10.1186/s12885-024-12803-8

39174921