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胶质母细胞瘤干细胞及其微环境。

Glioblastoma Stem Cells and Their Microenvironment.

机构信息

Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

出版信息

Adv Exp Med Biol. 2017;1041:119-140. doi: 10.1007/978-3-319-69194-7_7.

Abstract

Glioblastoma (GBM) is the most common primary malignant astrocytoma associated with a poor patient survival. Apart from arising de novo, GBMs also occur due to progression of slower growing grade III astrocytomas. GBM is characterized by extensive hypoxia, angiogenesis, proliferation and invasion. Standard treatment options such as surgical resection, radiation therapy and chemotherapy have increased median patient survival to 14.6 months in adults but recurrent disease arising from treatment resistant cancer cells often results in patient mortality. These treatment resistant cancer cells have been found to exhibit stem cell like properties. Strategies to identify or target these Glioblastoma Stem Cells (GSC) have proven to be unsuccessful so far. Studies on cancer stem cells (CSC) within GBM and other cancers have highlighted the importance of paracrine signaling networks within their microenvironment on the growth and maintenance of CSCs. The study of GSCs and their communication with various cell populations within their microenvironment is therefore not only important to understand the biology of GBMs but also to predict response to therapies and to identify novel targets which could stymy support to treatment resistant cancer cells and prevent disease recurrence. The purpose of this chapter is to introduce the concept of GSCs and to detail the latest findings indicating the role of various cellular subtypes within their microenvironment on their survival, proliferation and differentiation.

摘要

胶质母细胞瘤(GBM)是最常见的原发性恶性星形细胞瘤,患者生存预后较差。除了原发性肿瘤外,GBM 也可由生长缓慢的 III 级星形细胞瘤进展而来。GBM 的特征是广泛缺氧、血管生成、增殖和侵袭。手术切除、放疗和化疗等标准治疗方案使成年患者的中位生存时间延长至 14.6 个月,但由于治疗耐药癌细胞引起的复发性疾病常导致患者死亡。这些治疗耐药癌细胞被发现具有干细胞样特性。迄今为止,鉴定或靶向这些胶质母细胞瘤干细胞(GSC)的策略尚未取得成功。对 GBM 和其他癌症中的癌症干细胞(CSC)的研究强调了其微环境中的旁分泌信号网络对 CSC 的生长和维持的重要性。因此,研究 GSCs 及其与微环境中各种细胞群体的通讯不仅对于了解 GBM 的生物学特性很重要,而且对于预测对治疗的反应以及确定可能阻止治疗耐药癌细胞支持和预防疾病复发的新靶点也很重要。本章的目的是介绍 GSCs 的概念,并详细介绍最新研究结果,这些结果表明其微环境中的各种细胞亚型在 GSCs 的存活、增殖和分化中的作用。

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