Oligodendrocyte Progenitor Cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border.
Oligodendrocyte Progenitor Cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border.
复制标题
DOI：
10.1016/j.ebiom.2018.02.024
复制
发表时间：
2018-04
期刊：
影响因子：
11.1
通讯作者：
Yano S
中科院分区：
文献类型：
--
作者：
Hide T;Komohara Y;Miyasato Y;Nakamura H;Makino K;Takeya M;Kuratsu JI;Mukasa A;Yano S
胶质母细胞瘤（GBM）通常发生于成人脑白质。即使在完全切除后，GBM也会在肿瘤切除腔周围复发，在那里GBM细胞获得化学放射耐药性。肿瘤边界微环境的表征对于改善GBM患者的预后至关重要。在这里，我们通过miRNA芯片比较了来自肿瘤、肿瘤边缘和周围样品中的miRNA （miRNA）表达。肿瘤边界表达较高的前3位mirna与少突胶质细胞分化有关，病理上少突胶质细胞谱系在边界增加，巨噬细胞和小胶质细胞也在边界共定位。少突胶质细胞祖细胞（oligodendrocytes progenitor cells, OPCs）和巨噬细胞培养的培养基诱导GBM细胞的干性和化学放射抗性，类似于FGF1、EGF和HB-EGF、IL-1β产生的效果，分别对应于OPCs和巨噬细胞。因此，OPCs和巨噬细胞/小胶质细胞可能在肿瘤边界形成胶质瘤干细胞生态位，代表了预防复发的有希望的靶点。在全切除加放化疗后，大多数胶质母细胞瘤在切除腔周围的白质中复发。在肿瘤边缘表现出特征性高表达的mirna与少突胶质细胞分化有关。少突胶质细胞祖细胞和巨噬细胞的增加增强了胶质瘤细胞的干性和化学放射抗性。胶质母细胞瘤（GBM）发生于成人脑部，具有快速生长和侵袭的特点。尽管强化治疗，平均5年生存率仍<10%。大多数GBM病例即使在MRI观察到的钆增强病灶完全切除后也会局部复发，这表明化疗放射耐药的GBM细胞在那里存活。microrna在肿瘤边缘的高表达与少突胶质细胞的分化有关。少突胶质细胞祖细胞（OPCs）和巨噬细胞/小胶质细胞在肿瘤边界增加，并在体内诱导GBM细胞的干性和化学放射耐药。因此，OPCs和巨噬细胞/小胶质细胞形成了特征性的微环境，可能是预防GBM复发的有希望的靶点。
Glioblastoma (GBM) usually develops in adult brain white matter. Even after complete resection, GBM recurs around the tumor removal cavity, where GBM cells acquire chemo-radioresistance. Characterization of the tumor border microenvironment is critical for improving prognosis in patients with GBM. Here, we compared microRNA (miRNA) expression in samples from the tumor, tumor border, and periphery by miRNA microarray. The top three of miRNAs showing higher expression in the tumor border were related to oligodendrocyte differentiation, and pathologically oligodendrocyte lineage cells were increased in the border, where macrophages and microglia also colocalized. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, similar to that produced by FGF1, EGF and HB-EGF, IL-1β, corresponding to OPCs and macrophages, respectively. Thus, OPCs and macrophages/microglia may form a glioma stem cell niche at the tumor border, representing a promising target for prevention of recurrence. Most cases of glioblastoma recur in white matter around the removal cavity after total resection plus chemo-radiotherapy. miRNAs showing characteristically higher expression in the tumor border were related to oligodendrocyte differentiation. Increased oligodendrocyte progenitor cells and macrophages enhance stemness and chemo-radioresistance in glioma cells. Glioblastoma (GBM) occurs in adult brain and shows rapid growth and invasion. Despite intensive treatment, the mean 5-year survival rate is still <10%. Most cases of GBM recur locally even after total resection of gadolinium-enhanced lesions observed with MRI, indicating that chemo-radioresistant GBM cells survive there. MicroRNAs showing characteristically higher expression in the tumor border were related to oligodendrocyte differentiation. Oligodendrocyte progenitor cells (OPCs) and macrophages/microglia increased at tumor borders, and induced stemness and chemo-radioresistance in GBM cells in vivo. Thus, OPCs and macrophages/microglia formed characteristic microenvironments and may be promising targets to prevent GBM recurrence.
登录
查看更多内容
影响因子：
3.7
作者：
Ishii A;Kimura T;Sadahiro H;Kawano H;Takubo K;Suzuki M;Ikeda E
通讯作者：
Ikeda E
影响因子：
1.9
作者：
Hide T;Makino K;Nakamura H;Yano S;Anai S;Takezaki T;Kuroda J;Shinojima N;Ueda Y;Kuratsu J
通讯作者：
Kuratsu J
影响因子：
4.3
作者：
Barca-Mayo O;Lu QR
通讯作者：
Lu QR
影响因子：
5.7
作者：
Aihara A;Abe N;Saruhashi K;Kanaki T;Nishino T
通讯作者：
Nishino T
影响因子：
5.2
作者：
Hide, Takuichiro;Takezaki, Tatsuya;Kondo, Toru
通讯作者：
Kondo, Toru