Phenotypic Transition as a Survival Strategy of Glioma.
Phenotypic Transition as a Survival Strategy of Glioma.
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DOI：
10.2176/nmc.ra.2016-0077
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发表时间：
2016-07-15
影响因子：
1.9
通讯作者：
Date I
中科院分区：
文献类型：
--
作者：
Ichikawa T;Otani Y;Kurozumi K;Date I
恶性胶质瘤的特征是快速增殖、侵袭周围中枢神经系统组织和异常血管形成。越来越多的证据表明，胶质瘤比以前认为的更复杂，因为每个肿瘤都包含相当大的肿瘤内异质性，具有遗传和表型不同的亚克隆的混合物。肿瘤内和肿瘤间的异质性被认为是限制恶性胶质瘤治疗进展的关键因素。最近神经胶质瘤的基因分型和表达谱分析允许创建基于与定义的表达特征的相似性将肿瘤分配到亚型的分类方案。此外，恶性胶质瘤在复发和进展时经常改变其生物学特征。胶质瘤细胞抵抗诸如缺氧和代谢应激的不利条件的能力对于持续的肿瘤生长是必需的，并且强烈地影响肿瘤行为。一般而言，神经胶质瘤细胞处于两种表型类别中的一种：具有血管生成的较高增殖活性，或具有减弱的增殖能力的较高迁移活性。此外，他们根据情况切换表型类别。迄今为止，已采用多维方法来阐明胶质瘤表型转变的机制。胶质瘤的表型转变涉及多种分子和信号通路，它们之间可能存在串扰。本文就胶质瘤细胞的分子异质性和表型异质性以及表型异质性与胶质瘤增殖、血管生成和侵袭的关系作一综述。更好地理解胶质瘤表型转变的分子机制可能为靶向治疗策略提供新的见解。
Malignant glioma is characterized by rapid proliferation, invasion into surrounding central nervous system tissues, and aberrant vascularization. There is increasing evidence that shows gliomas are more complex than previously thought, as each tumor comprises considerable intratumoral heterogeneity with mixtures of genetically and phenotypically distinct subclones. Heterogeneity within and across tumors is recognized as a critical factor that limits therapeutic progress for malignant glioma. Recent genotyping and expression profiling of gliomas has allowed for the creation of classification schemes that assign tumors to subtypes based on similarity to defined expression signatures. Also, malignant gliomas frequently shift their biological features upon recurrence and progression. The ability of glioma cells to resist adverse conditions such as hypoxia and metabolic stress is necessary for sustained tumor growth and strongly influences tumor behaviors. In general, glioma cells are in one of two phenotypic categories: higher proliferative activity with angiogenesis, or higher migratory activity with attenuated proliferative ability. Further, they switch phenotypic categories depending on the situation. To date, a multidimensional approach has been employed to clarify the mechanisms of phenotypic shift of glioma. Various molecular and signaling pathways are involved in phenotypic shifts of glioma, possibly with crosstalk between them. In this review, we discuss molecular and phenotypic heterogeneity of glioma cells and mechanisms of phenotypic shifts in regard to the glioma proliferation, angiogenesis, and invasion. A better understanding of the molecular mechanisms that underlie phenotypic shifts of glioma may provide new insights into targeted therapeutic strategies.