Lewis Kate Marie, Petritsch Claudia
Department of Neurological Surgery, University of California San Francisco, San Francisco 94158, CA, USA.
Department of Neurological Surgery, University of California San Francisco, San Francisco 94158, CA, USA ; Brain Tumor Research Center, UCSF Helen Diller Comprehensive Cancer Center, UCSF Ely and Edythe Broad Institute of Regeneration Medicine.
Transl Neurosci. 2013 Dec;4(4):484-503. doi: 10.2478/s13380-013-0148-8.
Glioma is a heterogeneous disease process with differential histology and treatment response. It was previously thought that the histological features of glial tumors indicated their cell of origin. However, the discovery of continuous neuro-gliogenesis in the normal adult brain and the identification of brain tumor stem cells within glioma have led to the hypothesis that these brain tumors originate from multipotent neural stem or progenitor cells, which primarily divide asymmetrically during the postnatal period. Asymmetric cell division allows these cell types to concurrently self-renew whilst also producing cells for the differentiation pathway. It has recently been shown that increased symmetrical cell division, favoring the self-renewal pathway, leads to oligodendroglioma formation from oligodendrocyte progenitor cells. In contrast, there is some evidence that asymmetric cell division maintenance in tumor stem-like cells within astrocytoma may lead to acquisition of treatment resistance. Therefore cell division mode in normal brain stem and progenitor cells may play a role in setting tumorigenic potential and the type of tumor formed. Moreover, heterogeneous tumor cell populations and their respective cell division mode may confer differential sensitivity to therapy. This review aims to shed light on the controllers of cell division mode which may be therapeutically targeted to prevent glioma formation and improve treatment response.
胶质瘤是一种具有不同组织学特征和治疗反应的异质性疾病过程。以前人们认为胶质肿瘤的组织学特征表明了其起源细胞。然而，正常成人大脑中持续神经胶质发生的发现以及胶质瘤内脑肿瘤干细胞的鉴定，导致了这样一种假说，即这些脑肿瘤起源于多能神经干细胞或祖细胞，它们在出生后主要进行不对称分裂。不对称细胞分裂使这些细胞类型能够同时自我更新，同时也产生用于分化途径的细胞。最近有研究表明，增加对称细胞分裂，有利于自我更新途径，会导致少突胶质前体细胞形成少突胶质细胞瘤。相反，有一些证据表明，星形细胞瘤内肿瘤干细胞样细胞中不对称细胞分裂的维持可能导致获得治疗抗性。因此，正常脑干细胞和祖细胞中的细胞分裂模式可能在设定致瘤潜能和形成的肿瘤类型方面发挥作用。此外，异质性肿瘤细胞群体及其各自的细胞分裂模式可能赋予对治疗的不同敏感性。这篇综述旨在阐明细胞分裂模式的调控因子，这些调控因子可能成为治疗靶点，以预防胶质瘤形成并改善治疗反应。
