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星形胶质细胞,胶质母细胞瘤微环境的后起之秀。

Astrocytes, the rising stars of the glioblastoma microenvironment.

机构信息

Department of Biochemistry and Biomedicine, University of Sussex, School of Life Sciences, Brighton, United Kingdom.

Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom.

出版信息

Glia. 2019 May;67(5):779-790. doi: 10.1002/glia.23520. Epub 2018 Sep 21.

Abstract

Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in-depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.

摘要

胶质母细胞瘤(GBM)是一种侵袭性的原发性肿瘤,每年在全球导致数千人死亡。尽管目前有可用的治疗方法,但 GBM 患者的平均生存时间仍低于 20 个月。GBM 细胞与其基质对应物的相互作用对肿瘤的发展至关重要。星形胶质细胞是神经胶质细胞,约占所有脑细胞的 50%,因此很可能与 GBM 细胞直接接触。由于其他肿瘤细胞类型可以劫持成纤维细胞或免疫细胞来促进肿瘤生长,因此 GBM 细胞实际上可以激活星形胶质细胞,即肿瘤相关星形胶质细胞(TAAs),以促进 GBM 在健康组织中的浸润。TAAs 已被证明参与 GBM 细胞的生长和对放疗或化疗(即替莫唑胺)的有限反应。然而,尽管癌症研究界的兴趣正在增加,但 TAAs 在 GBM 发展中的作用仍被忽视。然而,深入了解 TAAs 影响 GBM 进展的机制可能会导致新的治疗策略的发展。因此,本文报告了 TAAs 最近被描述参与 GBM 进展的不同阶段,包括肿瘤细胞的增殖/浸润和对治疗的耐药性,特别是通过细胞外囊泡的活性。

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