Neuroblastoma-secreted exosomes carrying miR-375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells
Neuroblastoma-secreted exosomes carrying miR-375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells
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DOI：
10.1080/20013078.2020.1774144
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Di Giannatale, Angela
中科院分区：
文献类型：
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作者：
Colletti, Marta;Tomao, Luigi;Di Giannatale, Angela
骨髓（BM）是神经母细胞瘤（NB）转移的主要靶器官，其受累与不良结局相关。然而，NB细胞侵入BM的机制在很大程度上是未知的。肿瘤微环境是肿瘤进展的关键因素，间充质基质细胞（MSC）已被认为是相关肿瘤基质的基本组成部分。在这里，我们表明，骨髓受累的NB患者分离的骨髓间充质干细胞表现出更大的成骨潜能比骨髓间充质干细胞从非浸润。我们发现BM转移源性NB细胞系分泌更高水平的外泌体miR-375，其促进MSC的成骨分化。值得注意的是，临床数据表明高水平的miR-375与NB患者的BM转移相关。我们的研究结果确实表明，外泌体miR-375在决定BM中有利的微环境以促进转移进展中的潜在作用。因此，miR-375可能代表一种新的生物标志物和BM受累NB患者的潜在靶点。
Bone marrow (BM) is the major target organ for neuroblastoma (NB) metastasis and its involvement is associated with poor outcome. Yet, the mechanism by which NB cells invade BM is largely unknown. Tumour microenvironment represents a key element in tumour progression and mesenchymal stromal cells (MSCs) have been recognized as a fundamental part of the associated tumour stroma. Here, we show that BM-MSCs isolated from NB patients with BM involvement exhibit a greater osteogenic potential than MSCs from non-infiltrated BM. We show that BM metastasis-derived NB-cell lines secrete higher levels of exosomal miR-375, which promotes osteogenic differentiation in MSCs. Of note, clinical data demonstrate that high level of miR-375 correlates with BM metastasis in NB patients. Our findings suggest, indeed, a potential role for exosomal miR-375 in determining a favourable microenvironment in BM to promote metastatic progression. MiR-375 may, thus, represent a novel biomarker and a potential target for NB patients with BM involvement.