Harland Abigail J, Perks Claire M
Cancer Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol BS10 5NB, UK.
Int J Mol Sci. 2025 May 15;26(10):4749. doi: 10.3390/ijms26104749.
Glioblastoma is a fatal and aggressive cancer with no cure. It is becoming increasingly clear that glioblastoma initiation is a result of adult neural stem cell (NSC) transformation-most likely those within the subventricular zone (SVZ). Indeed, transcriptomic analysis indicates that glioblastomas are reminiscent of a neurodevelopmental hierarchy, in which neural stem and progenitor markers are widely expressed by tumour stem-like cells. However, NSC fates and the cues that drive them are poorly understood. Studying the crosstalk within NSC niches may better inform our understanding of glioblastoma initiation and development. Insulin-like growth factor binding protein 2 (IGFBP-2) has a well-established prognostic role in glioblastoma, and cell-based mechanistic studies show the independent activation of downstream oncogenic pathways. However, IGFBP-2 is more commonly recognised as a modulator of insulin-like growth factors (IGFs) for receptor tyrosine kinase signal propagation or attenuation. In the adult human brain, both IGFBP-2 and IGF-II expression are retained in the choroid plexus (ChP) and secreted into the cerebral spinal fluid (CSF). Moreover, secretion by closely associated cells and NSCs themselves position IGFBP-2 and IGF-II as interesting factors within the NSC niche. In this review, we will highlight the experimental findings that show IGFBP-2 and IGF-II influence NSC behaviour. Moreover, we will link this to glioblastoma biology and demonstrate the requirement for further analysis of these factors in glioma stem cells (GSCs).
胶质母细胞瘤是一种致命的侵袭性癌症，无法治愈。越来越明显的是，胶质母细胞瘤的起始是成年神经干细胞（NSC）转化的结果——很可能是脑室下区（SVZ）内的那些细胞。事实上，转录组分析表明，胶质母细胞瘤让人联想到一种神经发育层次结构，其中神经干细胞和祖细胞标志物在肿瘤干细胞样细胞中广泛表达。然而，人们对神经干细胞的命运及其驱动因素了解甚少。研究神经干细胞微环境中的相互作用可能有助于我们更好地理解胶质母细胞瘤的起始和发展。胰岛素样生长因子结合蛋白2（IGFBP - 2）在胶质母细胞瘤中具有公认的预后作用，基于细胞的机制研究表明其可独立激活下游致癌途径。然而，IGFBP - 2更常被认为是胰岛素样生长因子（IGFs）的调节剂，用于受体酪氨酸激酶信号的传播或衰减。在成人大脑中，IGFBP - 2和IGF - II的表达都保留在脉络丛（ChP）中，并分泌到脑脊液（CSF）中。此外，紧密相关细胞和神经干细胞自身的分泌使IGFBP - 2和IGF - II成为神经干细胞微环境中有趣的因素。在这篇综述中，我们将重点介绍显示IGFBP - 2和IGF - II影响神经干细胞行为的实验结果。此外，我们将把这与胶质母细胞瘤生物学联系起来，并证明在胶质瘤干细胞（GSCs）中进一步分析这些因素的必要性。
