Biogenesis of a new type of extracellular vesicles in gastrointestinal stromal tumors: ultrastructural profiles of spheresomes.

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.