Department of Biomedical Engineering, Columbia University, New York, New York,USA; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain.
Department of Biomedical Engineering, Columbia University, New York, New York,USA.
Transl Res. 2021 Nov;237:82-97. doi: 10.1016/j.trsl.2021.06.006. Epub 2021 Jul 2.
Neuroblastoma (NB) is the most common extracranial pediatric solid cancer originating from undifferentiated neural crest cells. NB cells express EZH2 and GLI1 genes that are known to maintain the undifferentiated phenotype of cancer stem cells (CSC) in NB. Recent studies suggest that tumor-derived extracellular vesicles (EVs) can regulate the transformation of surrounding cells into CSC by transferring tumor-specific molecules they contain. However, the horizontal transfer of EVs molecules in NB remains largely unknown. We report the analysis of NB-derived EVs in bioengineered models of NB that are based on a collagen 1/hyaluronic acid scaffold designed to mimic the native tumor niche. Using these models, we observed an enrichment of GLI1 and EZH2 mRNAs in NB-derived EVs. As a consequence of the uptake of NB-derived EVs, the host cells increased the expression levels of GLI1 and EZH2. These results suggest the alteration of the expression profile of stromal cells through an EV-based mechanism, and point the GLI1 and EZH2 mRNAs in the EV cargo as diagnostic biomarkers in NB.
神经母细胞瘤（NB）是最常见的起源于未分化神经嵴细胞的颅外小儿实体瘤。NB 细胞表达 EZH2 和 GLI1 基因，这些基因被认为能维持 NB 中癌症干细胞（CSC）的未分化表型。最近的研究表明，肿瘤来源的细胞外囊泡（EVs）可以通过转移其中包含的肿瘤特异性分子，调节周围细胞向 CSC 的转化。然而，NB 中 EVs 分子的水平转移在很大程度上仍不清楚。我们报告了在基于胶原蛋白 1/透明质酸支架的 NB 生物工程模型中分析 NB 衍生的 EVs，该支架旨在模拟天然肿瘤微环境。使用这些模型，我们观察到 NB 衍生的 EVs 中 GLI1 和 EZH2 mRNA 的富集。由于 NB 衍生的 EVs 的摄取，宿主细胞增加了 GLI1 和 EZH2 的表达水平。这些结果表明通过 EV 为基础的机制改变了基质细胞的表达谱，并指出 EV 货物中的 GLI1 和 EZH2 mRNA 作为 NB 的诊断生物标志物。
