Growth and differentiation factor 15 regulates PD-L1 expression in glioblastoma
| Autor: | Jun Fu, Haiqing Peng, Rongrong Zhou, Zhanzhan Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene knockdown biology medicine.diagnostic_test Growth differentiation factor Transforming growth factor beta superfamily medicine.disease nervous system diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Western blot Cell culture 030220 oncology & carcinogenesis Glioma PD-L1 medicine biology.protein Cancer research GDF15 |
| Zdroj: | Cancer Management and Research. 11:2653-2661 |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s192095 |
| Popis: | Background: Gliomablastoma multiforme (GBM) is the most fatal form of all brain cancers in human with no successful treatment available. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand predominantly expressed by tumor cells. Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in tissue development and cancer. Purpose: To investigat the expression of GDFs in GBMs, and explored the potential regulatory role of GDFs on PD-L1 expression in GBMs. Methods: GEO2R program were analyzed for the mRNA expression data of GDFs in GSE4290 dataset. Analysis of TCGA GBM datasets were further determined the relationship between GDFs and PD-L1. Western blot Western blot was used to detect the expression of PD-L1 in GBM cell lines. Results: GDFs displayed differential patterns of expression with GDF15 and myostatin (MSTN) highly enriched in GBM tissues. We also identified GDF15 as a novel regulator that induces PD-L1 expression in GBM cells. Consistently, GDF15 expression correlated with PD-L1 in TCGA GBM dataset. Further, GDF15 enhanced PD-L1 expression via Smad2/3 pathway in GBM cell line U87, U251 and SHG44, which was inhibited by Smad2/3 inhibitor SIS3. Knockdown of GDF15 attenuated Smad2/3 signaling and reduced PD-L1 expression in A172 and GIC6 glioma cells. Conclusion: GDF15 might be a novel regulator of PD-L1 expression in GBMs; targeting GDF15/PD-L1 pathway might be a promising therapeutic approach for GBM patients. |
| Databáze: | OpenAIRE |
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