BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression
BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression
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DOI：
10.1172/jci66517
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发表时间：
2013-04-01
影响因子：
15.9
通讯作者：
Ghobrial, Irene M.
中科院分区：
文献类型：
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作者：
Roccaro, Aldo M.;Sacco, Antonio;Ghobrial, Irene M.
骨髓间充质基质细胞(BM-MSCs)支持多发性骨髓瘤(MM)细胞生长，但对BM微环境在多发性骨髓瘤(MM)致癌中的作用机制知之甚少。细胞与细胞之间的通讯是由外切体介导的。在这项研究中，我们发现MM BM-MSCs释放的外体被转移到MM细胞，从而导致体内肿瘤生长的调节。MM和正常BM-MSCs的外体microRNA(MiR)含量不同，肿瘤抑制因子miR-15a的含量较低。此外，MM BM-MSC来源的外切体与来源细胞的外切体相比，具有更高水平的致癌蛋白、细胞因子和黏附分子。重要的是，尽管MM BM-MSC来源的外切体促进了MM肿瘤的生长，但正常的BM-MSC外切体抑制了MM细胞的生长。综上所述，这些体外和体内研究表明，外切体从BM-MSCs到克隆性浆细胞的转移代表了一种以前未被描述的独特机制，突出了BM-MSCs在MM疾病进展中的贡献。
BM mesenchymal stromal cells (BM-MSCs) support multiple myeloma (MM) cell growth, but little is known about the putative mechanisms by which the BM microenvironment plays an oncogenic role in this disease. Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR) content differed between MM and normal BM-MSCs, with a lower content of the tumor suppressor miR-15a. In addition, MM BM-MSC-derived exosomes had higher levels of oncogenic proteins, cytokines, and adhesion molecules compared with exosomes from the cells of origin. Importantly, whereas MM BM-MSC-derived exosomes promoted MM tumor growth, normal BM-MSC exosomes inhibited the growth of MM cells. In summary, these in vitro and in vivo studies demonstrated that exosome transfer from BM-MSCs to clonal plasma cells represents a previously undescribed and unique mechanism that highlights the contribution of BM-MSCs to MM disease progression.