論文 - 詳細
| RRC ID | 86843 |
|---|---|
| 著者 | Zheng Y, Yamamoto S, Ishii Y, Sang Y, Hamashima T, Van De N, Nishizono H, Inoue R, Mori H, Sasahara M. |
| タイトル | Glioma-Derived Platelet-Derived Growth Factor-BB Recruits Oligodendrocyte Progenitor Cells via Platelet-Derived Growth Factor Receptor-α and Remodels Cancer Stroma. |
| ジャーナル | Am J Pathol |
| Abstract |
Glioma is an aggressive and incurable disease, and is frequently accompanied by augmented platelet-derived growth factor (PDGF) signaling. Overexpression of PDGF-B ligand characterizes a specific subclass of glioblastoma multiforme, but the significance of the ligand remains to be elucidated. For this end, we implanted a glioma-cell line transfected with PDGF-BB-overexpressing vector (GL261-PDGF-BB) or control vector (GL261-vector) into wild-type mouse brain, and examined the effect of glioma-derived PDGF on the tumor microenvironment. The volume of GL261-PDGF-BB rapidly increased compared with GL261-vector. Recruitment of many PDGF receptor (PDGFR)-α and Olig2-positive oligodendrocyte precursor cells and frequent hemorrhages were observed in GL261-PDGF-BB but not in GL261-vector. We then implanted GL261-PDGF-BB into the mouse brain with and without Pdgfra gene inactivation, corresponding to PDGFRα-knockout (KO) and Flox mice, respectively. The recruitment of oligodendrocyte precursor cells was largely suppressed in PDGFRα-KO than in Flox, whereas the volume of GL261-PDGF-BB was comparable between the two genotypes. Frequent hemorrhage and increased IgG-leakage were associated with aberrant vascular structures within the area where many recruited oligodendrocyte precursor cells accumulated in Flox. In contrast, these vascular phenotypes were largely normalized in PDGFRα-KO. Increased matrix metalloproteinase-9 in recruited oligodendrocyte precursor cells and decreased claudin-5 in vasculature may underlie the vascular abnormality. Glioma-derived PDGF-B signal induces cancer stroma characteristically seen in high-grade glioma, and should be therapeutically targeted to improve cancer microenvironment. |
| 巻・号 | 186(5) |
| ページ | 1081-91 |
| 公開日 | 2016-5-1 |
| DOI | 10.1016/j.ajpath.2015.12.020 |
| PII | S0002-9440(16)00082-1 |
| PMID | 26945107 |
| MeSH | Animals Antineoplastic Agents, Hormonal / pharmacology Brain Neoplasms / drug therapy Brain Neoplasms / pathology* Capillary Permeability / physiology Cell Line, Tumor Cerebral Hemorrhage / etiology Collagen / physiology Female Gene Knockout Techniques Genetic Vectors Glioblastoma / drug therapy Glioblastoma / pathology* Male Mice, Inbred C57BL Mice, Knockout Neoplasm Transplantation Oligodendroglia / physiology* Phenotype Proto-Oncogene Proteins c-sis / physiology* Stem Cells / physiology* Tamoxifen / pharmacology Transfection Tumor Burden |
| IF | 3.491 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01834 |