Junquera Concepción, Castiella Tomás, Muñoz Guillermo, Fernández-Pacheco Rodrigo, Luesma M José, Monzón Marta
Faculty of Medicine, Institute for Health Research Aragón (IIS), C/Domingo Miral s/n, 50009, Saragossa, Spain.
University Hospital Lozano Blesa, University of Zaragoza, Saragossa, Spain.
Histochem Cell Biol. 2016 Nov;146(5):557-567. doi: 10.1007/s00418-016-1460-5. Epub 2016 Jul 4.
Extracellular vesicles (EVs) have emerged as an intercellular communication mediator in cancer. They seem to be involved in tumor processes by means of transformation of surrounding cells previous to metastasis by transferring miRNAs and oncogenic proteins. It is known that EVs, depending on their source, can be exosomes or ectosomes. Although the first type constitutes a specific population formed from the endosomal system, via multivesicular bodies, the ectosome biogenesis is not yet well known. In this study, we report a new type of EVs which has been termed spheresomes. While exosomes come from multivesicular bodies and ectosomes from direct budding of plasma membrane, spheresomes present a new mechanism of shedding from a spherical membrane structure which we have named multivesicular spheres. These EVs are first described in gastrointestinal stromal tumor cells in the present study. But moreover, these new membrane spherical structures appear not only next to tumoral cells but also different distances from them. Since some other authors have evidenced oncogenic KIT-containing EVs, it is also suggested here that surrounding cells uptake of these first described EVs, GIST-derived spheresomes, could induce tumor invasiveness. That is why the prevention of signaling processes developed by these new EVs may represent an alternative approach for GIST treatment.
细胞外囊泡（EVs）已成为癌症中细胞间通讯的介质。它们似乎通过在转移前转移微小RNA（miRNAs）和致癌蛋白来转化周围细胞，从而参与肿瘤进程。已知EVs根据其来源可分为外泌体或微泡。虽然第一种类型是由内体系统通过多囊泡体形成的特定群体，但微泡的生物发生机制尚不清楚。在本研究中，我们报告了一种新型的EVs，称为球状体。外泌体来自多囊泡体，微泡来自质膜的直接出芽，而球状体呈现出一种从我们称为多囊泡球的球形膜结构脱落的新机制。在本研究中，这些EVs首次在胃肠道间质瘤细胞中被描述。此外，这些新的膜球形结构不仅出现在肿瘤细胞附近，而且与肿瘤细胞有不同的距离。由于其他一些作者已经证明了含有致癌性KIT的EVs，因此这里还提出，周围细胞摄取这些首次描述的EVs，即胃肠道间质瘤来源的球状体，可能会诱导肿瘤侵袭性。这就是为什么阻断这些新型EVs所引发的信号传导过程可能代表一种治疗胃肠道间质瘤的替代方法。
