| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC01834 |
