Muñoz Diana Marcela, Guha Abhijit
The Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
Oncotarget. 2011 Aug;2(8):590-8. doi: 10.18632/oncotarget.319.
Glioblastoma multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors, with a median survival of 14-16 months despite optimal surgery, radiation and chemotherapy. A reason for this dismal prognosis is insufficient understanding of the ontogeny of GBMs, which are highly heterogeneous at a pathological level. This pathological diversity, between and within GBMs as well as varying grades of gliomas, has not been fully explained solely on the grounds of oncogenic stimulus. Interaction with the tumor microenvironment is likely a source of this pathological heterogeneity, as well as the inherent characteristics of the tumor cell of origin. Currently, controversy exists on whether the initial transformed cell is a differentiated astrocyte, progenitor or neural stem cell. Putative cancer stem cells (CSCs), which have features of normal stem cell plus the ability to recapitulate the tumor phenotype in vivo in small numbers, have been identified from a variety of solid human cancers, including GBMs. Evidence suggesting that regions harboring normal stem cells in the adult CNS, such as the subventricular zone and the dentate gyrus, are more prone to viral and chemical oncogenesis, is supportive of the hypothesis that brain tumors arise from stem cells. However, it is still to be determined whether the appearance of brain tumor stem cells (BTSC) is the cause or consequence of tumor initiation and progression. This review discusses emerging evidence highlighting the relevance of the state of differentiation and regional heterogeneity in the ontogeny of GBM. This is an area of high interest in cancer in general, with potential significant therapeutic and prognostic implications.
多形性胶质母细胞瘤（GBM）是人类原发性中枢神经系统（CNS）肿瘤中最常见且致命的肿瘤，尽管进行了最佳的手术、放疗和化疗，其平均生存期仍为14 - 16个月。这种预后不佳的一个原因是对GBM的发生发展了解不足，GBM在病理水平上具有高度异质性。这种病理多样性，在GBM之间以及内部，以及不同级别的胶质瘤之间，仅基于致癌刺激尚未得到充分解释。与肿瘤微环境的相互作用可能是这种病理异质性的一个来源，以及肿瘤起源细胞的固有特征。目前，关于初始转化细胞是分化的星形胶质细胞、祖细胞还是神经干细胞存在争议。从包括GBM在内的多种实体人类癌症中已鉴定出假定的癌症干细胞（CSC），其具有正常干细胞的特征以及少量在体内重现肿瘤表型的能力。有证据表明，成人大脑中含有正常干细胞的区域，如脑室下区和齿状回，更容易发生病毒和化学致癌作用，这支持了脑肿瘤起源于干细胞的假说。然而，脑肿瘤干细胞（BTSC）的出现是肿瘤起始和进展的原因还是结果仍有待确定。本综述讨论了新出现的证据，强调了分化状态和区域异质性在GBM发生发展中的相关性。这总体上是癌症领域一个备受关注的领域，具有潜在的重大治疗和预后意义。
