Albert Thomas K, Interlandi Marta, Sill Martin, Graf Monika, Moreno Natalia, Menck Kerstin, Rohlmann Astrid, Melcher Viktoria, Korbanka Sonja, Meyer Zu Hörste Gerd, Lautwein Tobias, Frühwald Michael C, Krebs Christian F, Holdhof Dörthe, Schoof Melanie, Bleckmann Annalen, Missler Markus, Dugas Martin, Schüller Ulrich, Jäger Natalie, Pfister Stefan M, Kerl Kornelius
Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.
Institute of Medical Informatics, Westphalian-Wilhelms-University (WWU) Münster, Münster, Germany.
Neuro Oncol. 2021 Apr 12;23(4):586-598. doi: 10.1093/neuonc/noaa254.
Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises 4 subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts.
We used a combination of single-cell transcriptomics, cell culture models and biophysical methods such as nanoparticle tracking analysis and electron microscopy to investigate intercellular communication in the MB tumor niche.
Tumor cells of the sonic hedgehog (SHH)-MB subgroup show a differentiation blockade. These cells undergo extensive metabolic reprogramming. The gene expression profiles of individual tumor cells show a partial convergence with those of tumor-associated glial and immune cells. One possible cause is the transfer of extracellular vesicles (EVs) between cells in the tumor niche. We were able to detect EVs in co-culture models of MB tumor cells and oligodendrocytes. We also identified a gene expression signature, EVS, which shows overlap with the proteome profile of large oncosomes from prostate cancer cells. This signature is also present in MB patient samples. A high EVS expression is one common characteristic of tumors that occur in high-risk patients from different MB subgroups or subtypes.
With EVS, our study uncovered a novel gene expression signature that has a high prognostic significance across MB subgroups.
髓母细胞瘤（MB）是儿童期的一种恶性脑肿瘤。它包含4个具有不同临床行为的亚组。本研究的目的是在个体肿瘤水平以及大型患者队列中描绘MB的转录组图谱。
我们结合单细胞转录组学、细胞培养模型以及纳米颗粒追踪分析和电子显微镜等生物物理方法，来研究MB肿瘤微环境中的细胞间通讯。
音猬因子（SHH）-MB亚组的肿瘤细胞表现出分化阻滞。这些细胞经历广泛的代谢重编程。单个肿瘤细胞的基因表达谱与肿瘤相关神经胶质细胞和免疫细胞的基因表达谱部分趋同。一个可能的原因是肿瘤微环境中细胞之间细胞外囊泡（EVs）的转移。我们能够在MB肿瘤细胞和少突胶质细胞的共培养模型中检测到EVs。我们还鉴定出一种基因表达特征EVS，它与前列腺癌细胞大肿瘤小体的蛋白质组图谱有重叠。这种特征也存在于MB患者样本中。高EVS表达是来自不同MB亚组或亚型的高危患者中发生的肿瘤的一个共同特征。
通过EVS，我们的研究发现了一种新的基因表达特征，它在MB亚组中具有很高的预后意义。
