Glioma-derived extracellular vesicles promote tumor progression by conveying WT1
| Autor: | Yu Dong, Jiakang Zhang, Takeshi Yoshida, Shabierjiang Jiapaer, Ryouken Kimura, Taishi Tsutsui, Mitsutoshi Nakada, Rikinari Hanayama, Hemragul Sabit, Hironori Kawahara |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Angiogenesis Mice Nude Apoptosis Cell Communication Biology Extracellular Vesicles Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Glioma Gene expression Thrombospondin 1 Biomarkers Tumor Tumor Cells Cultured Tumor Microenvironment medicine Animals Humans WT1 Proteins Cell Proliferation Mice Inbred BALB C Tumor microenvironment Microglia Brain Neoplasms General Medicine Prognosis medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Carcinogenesis. 41:1238-1245 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgaa052 |
| Popis: | Glioma persists as one of the most aggressive primary tumors of the central nervous system. Glioma cells are known to communicate with tumor-associated macrophages/microglia via various cytokines to establish the tumor microenvironment. However, how extracellular vesicles (EVs), emerging regulators of cell–cell communication networks, function in this process is still elusive. We report here that glioma-derived EVs promote tumor progression by affecting microglial gene expression in an intracranial implantation glioma model mouse. The gene expression of thrombospondin-1 (Thbs1), a negative regulator of angiogenesis, was commonly downregulated in microglia after the addition of EVs isolated from different glioma cell lines, which endogenously expressed Wilms tumor-1 (WT1). Conversely, WT1-deficiency in the glioma-derived EVs significantly attenuated the Thbs1 downregulation and suppressed the tumor progression. WT1 was highly expressed in EVs obtained from the cerebrospinal fluid of human patients with malignant glioma. Our findings establish a novel model of tumor progression via EV-mediated WT1–Thbs1 intercellular regulatory pathway, which may be a future diagnostic or therapeutic target. |
| Databáze: | OpenAIRE |
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