星形胶质细胞
生物
U87型
基因签名
癌症研究
胶质瘤
细胞生长
细胞培养
骨膜炎
体内
细胞
基因表达
细胞生物学
神经科学
基因
中枢神经系统
遗传学
细胞外基质
作者
Alessandro Mega,Mette Hartmark Nilsen,Lina Leiss,Nicholas P. Tobin,Hrvoje Miletić,Linda Sleire,Carina Strell,Sven Nelander,Cecilia Krona,Daniel Hägerstrand,Per Øyvind Enger,Monica Nistér,Arne Östman
出处
期刊:Glia
[Wiley]
日期:2019-09-11
卷期号:68 (2): 316-327
被引量:81
摘要
Abstract Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies. Co‐culture techniques were used to investigate the GBM growth enhancing potential of astrocytes. Cell sorting and RNA sequencing were used to generate a GBM‐associated astrocyte signature and to investigate astrocyte‐induced GBM genes. A NOD scid GBM mouse model was used for in vivo studies. A gene signature reflecting GBM‐activated astrocytes was associated with poor prognosis in the TCGA GBM dataset. Two genes, periostin and serglycin, induced in GBM cells upon exposure to astrocytes were expressed at higher levels in cases with high “astrocyte signature score”. Astrocytes were shown to enhance glioblastoma cell growth in cell lines and in a patient‐derived culture, in a manner dependent on cell–cell contact and involving increased cell proliferation. Furthermore, co‐injection of astrocytes with glioblastoma cells reduced survival in an orthotopic GBM model in NOD scid mice. In conclusion, this study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies.
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