Pokorná Markéta, Hudec Michael, Juříčková Iva, Vácha Michael, Polívková Zdeňka, Kútna Viera, Pala Jan, Ovsepian Saak V, Černá Marie, O'Leary Valerie Bríd
Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, Vinohrady 10000 Prague, Czech Republic.
Department of Experimental Neurobiology, National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic.
Brain Sci. 2021 Jun 18;11(6):812. doi: 10.3390/brainsci11060812.
Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs and in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.
多形性胶质母细胞瘤(GBM)是一种预后较差的原发性脑癌,现有治疗方法基本上仍属姑息性治疗。由于异质性肿瘤迅速复发,当前的GBM治疗失败,模型表明复发性生长源自治疗抗性胶质母细胞瘤干细胞样细胞(GSCs)。GSCs是否依赖于其周围微环境生态位的生存/增殖信号,特别是治疗后前沿周围的信号,仍然未知。在实验室中模拟人类GBM依赖于用于转化医学的代表性细胞系和异种移植模型。由于U87MG来源的差异以及对维甲酸治疗的不同增殖反应,本研究突出了使用这种代表性GBM细胞系的实验室科学家所面临的挑战。研究对全反式维甲酸(ATRA)的反应揭示了其对prominin-1干细胞标志物的隔离作用。在整个U87MG中普遍存在的ICAM-1被ATRA增强,这对化疗靶向研究具有重要意义。ATRA在前沿和建立的单层生长区微环境中触发了长链非编码RNA的多种表达模式。核型分析证实了源自欧洲的U87MG的雌性起源。传代培养U87MG揭示了存在反映该胶质母细胞瘤细胞系结构基因组改变的染色体异常。综合所有证据,本研究揭示了U87MG进一步的表型细微差别,这可能会误导寻求有助于攻克GBM这一难题的数据的研究人员。