Wlodarczyk Aneta, Grot Dagmara, Stoczynska-Fidelus Ewelina, Rieske Piotr
Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
J Oncol. 2020 Jul 22;2020:6783627. doi: 10.1155/2020/6783627. eCollection 2020.
Cellular origin of glioblastoma (GB) is constantly discussed and remains a controversial subject. Unfortunately, neurobiologists are not consistent in defining neural stem cells (NSC) complicating this issue even further. Nevertheless, some suggestions referring to GB origin can be proposed based on comparing GB to central nervous system (CNS) cells. Firstly, GB cells show differentiation pattern similar to GFAP positive neural cells, rather than classical (GFAP negative) NSC. GB cells in primary cultures become senescent , similar to GFAP positive neural progenitors, whereas classical NSC proliferate infinitely. Classical NSC apoptosis triggered by introduction of IDH1R132H undermines hypothesis stating that IDH-mutant (secondary) GB origins from these NSC. Analysis of biological role of typical IDH-wildtype (primary) GB oncogene such as EGFRvIII also favors GFAP positive cells rather than classical NSC as source of GB. Single-cell NGS and single-cell transcriptomics also suggest that GFAP positive cells are GB origin. Considering the above-mentioned and other discussed in articles data, we suggest that GFAP positive cells (astrocytes, radial glia, or GFAP positive neural progenitors) are more likely to be source of GB than classical GFAP negative NSC, and further assays should be focused on these cells. It is highly possible that several populations of tumor initiating cells (TIC) exist within GB, adjusting their phenotype and even genotype to various environmental conditions including applied therapy and periodically going through different TIC states as well as non-TIC state. This adjustment is driven by changes in number and types of amplicons. The existence of various populations of TIC would enable creating neoplastic foci in different environments and increase tumor aggressiveness.
胶质母细胞瘤（GB）的细胞起源一直是讨论的焦点，并且仍然是一个有争议的话题。不幸的是，神经生物学家在定义神经干细胞（NSC）方面并不一致，这使得这个问题更加复杂。然而，基于将GB与中枢神经系统（CNS）细胞进行比较，可以提出一些关于GB起源的建议。首先，GB细胞表现出与GFAP阳性神经细胞相似的分化模式，而不是经典的（GFAP阴性）NSC。原代培养中的GB细胞会衰老，类似于GFAP阳性神经祖细胞，而经典NSC则无限增殖。引入IDH1R132H引发的经典NSC凋亡削弱了IDH突变型（继发性）GB起源于这些NSC的假说。对典型的IDH野生型（原发性）GB癌基因如EGFRvIII的生物学作用分析也支持GFAP阳性细胞而非经典NSC作为GB的来源。单细胞NGS和单细胞转录组学也表明GFAP阳性细胞是GB的起源。考虑到上述文章中讨论的以及其他数据，我们认为GFAP阳性细胞（星形胶质细胞、放射状胶质细胞或GFAP阳性神经祖细胞）比经典的GFAP阴性NSC更有可能是GB的来源，并且进一步的检测应该集中在这些细胞上。GB内很可能存在多个肿瘤起始细胞（TIC）群体，它们会根据包括应用治疗在内的各种环境条件调整其表型甚至基因型，并定期经历不同的TIC状态以及非TIC状态。这种调整是由扩增子数量和类型的变化驱动的。不同TIC群体的存在将使肿瘤在不同环境中形成瘤灶并增加肿瘤侵袭性。
