کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5932129 1573368 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glioma-Derived Platelet-Derived Growth Factor-BB Recruits Oligodendrocyte Progenitor Cells via Platelet-Derived Growth Factor Receptor-α and Remodels Cancer Stroma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Glioma-Derived Platelet-Derived Growth Factor-BB Recruits Oligodendrocyte Progenitor Cells via Platelet-Derived Growth Factor Receptor-α and Remodels Cancer Stroma
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 186, Issue 5, May 2016, Pages 1081-1091
نویسندگان
, , , , , , , , , ,