Biamonte Filippo, Sica Gigliola, Filippini Antonio, D'Alessio Alessio
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino Gemelli", IRCCS, 00168 Roma, Italy.
Dipartimento di Scienze della Vita e Sanità Pubblica, Sezione di Istologia ed Embriologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino Gemelli", IRCCS, 00168 Roma, Italy.
Brain Sci. 2021 Jun 3;11(6):745. doi: 10.3390/brainsci11060745.
Glioblastoma (GBM) is the most aggressive and malignant form of primary brain cancer, characterized by an overall survival time ranging from 12 to 18 months. Despite the progress in the clinical treatment and the growing number of experimental data aimed at investigating the molecular bases of GBM development, the disease remains characterized by a poor prognosis. Recent studies have proposed the existence of a population of GBM cancer stem cells (CSCs) endowed with self-renewal capability and a high tumorigenic potential that are believed to be responsible for the resistance against common chemotherapy and radiotherapy treatments. Reelin is a large secreted extracellular matrix glycoprotein, which contributes to positioning, migration, and laminar organization of several central nervous system structures during brain development. Mutations of the reelin gene have been linked to disorganization of brain structures during development and behavioral anomalies. In this study, we explored the expression of reelin in GBM and its related peritumoral tissue and performed the same analysis in CSCs isolated from both GBM (GCSCs) and peritumoral tissue (PCSCs) of human patients. Our findings reveal (i) the higher expression of reelin in GBM compared to the peritumoral tissue by immunohistochemical analysis, (ii) the mRNA expression of both reelin and its adaptor molecule Dab1 in either CSC subtypes, although at a different extent; and (iii) the contribution of CSCs-derived reelin in the migration of human primary GBM cell line U87MG. Taken together, our data indicate that the expression of reelin in GBM may represent a potential contribution to the regulation of GBM cancer stem cells behavior, further stimulating the interest on the reelin pathway as a potential target for GBM treatment.
胶质母细胞瘤（GBM）是原发性脑癌中最具侵袭性和恶性的形式，其总生存时间为12至18个月。尽管临床治疗取得了进展，且旨在研究GBM发生分子基础的实验数据不断增加，但该疾病的预后仍然很差。最近的研究提出，存在一群具有自我更新能力和高致瘤潜力的GBM癌症干细胞（CSC），据信它们是导致对常见化疗和放疗产生抗性的原因。Reelin是一种大型分泌型细胞外基质糖蛋白，在脑发育过程中有助于几个中枢神经系统结构的定位、迁移和层状组织。Reelin基因的突变与发育过程中脑结构的紊乱和行为异常有关。在本研究中，我们探讨了Reelin在GBM及其相关瘤周组织中的表达，并对从人类患者的GBM（GCSC）和瘤周组织（PCSC）中分离出的CSC进行了同样的分析。我们的研究结果显示：（i）通过免疫组织化学分析，GBM中Reelin的表达高于瘤周组织；（ii）两种CSC亚型中均有Reelin及其衔接分子Dab1的mRNA表达，尽管程度不同；以及（iii）CSC衍生的Reelin对人原发性GBM细胞系U87MG迁移的作用。综上所述，我们的数据表明，GBM中Reelin的表达可能对GBM癌症干细胞行为的调节有潜在贡献，进一步激发了人们对Reelin通路作为GBM治疗潜在靶点的兴趣。
