| RRC ID |
63845
|
| 著者 |
Tsutsui T, Kawahara H, Kimura R, Dong Y, Jiapaer S, Sabit H, Zhang J, Yoshida T, Nakada M, Hanayama R.
|
| タイトル |
Glioma-derived extracellular vesicles promote tumor progression by conveying WT1.
|
| ジャーナル |
Carcinogenesis
|
| Abstract |
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.
|
| 巻・号 |
41(9)
|
| ページ |
1238-1245
|
| 公開日 |
2020-9-24
|
| DOI |
10.1093/carcin/bgaa052
|
| PII |
5848230
|
| PMID |
32463428
|
| MeSH |
Animals
Apoptosis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Brain Neoplasms / genetics
Brain Neoplasms / metabolism
Brain Neoplasms / pathology*
Cell Communication
Cell Proliferation
Extracellular Vesicles / metabolism
Extracellular Vesicles / pathology*
Gene Expression Regulation, Neoplastic
Glioma / genetics
Glioma / metabolism
Glioma / pathology*
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Microglia / metabolism
Microglia / pathology*
Prognosis
Tumor Cells, Cultured
Tumor Microenvironment / immunology
WT1 Proteins / genetics
WT1 Proteins / metabolism*
Xenograft Model Antitumor Assays
|
| IF |
4.603
|
| リソース情報 |
| ヒト・動物細胞 |
MG6(RCB2403) |
