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

Abstract

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.

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

“…The field of EV is rapidly developing, and new types of EVs are emerging such as large oncosome (35) and spheresome (36). Large oncosome is a group of EVs with atypically large size (1–10 μm in diameter).…”

“…Another new type of EV is termed spheresome. Spheresome was first identidied in the tissue of gastrointestinal stromal tumors by scanning transmission electron microscopy (36). These vesicles have lipid bilayer membrane with 40–125 nm in diameter.…”

Exosomes in cancer theranostic: Diamonds in the rough

“…8 Recently, a new type of EVs have been described in gastrointestinal stromal tumors called spheresomes. 9 All these vesicles types differ in their subcellular origin, their biophysical and/or biochemical properties, their receptors composition, and their content in soluble proteins and genetic material. As they contain some nanoliters of cytosol and expose at the outer space the same proteins than the parental cell, they are also considered as nanosized cells with a functional role in many biological processes.…”

Deciphering the role of ectosomes in cancer development and progression: focus on the proteome

“…Table 2 gives examples of molecular markers associated with ectosomes. Recently the existence of a new type of EVs termed sphereosomes has been postulated [9]. The presence of these structures, between 40 and 125 nm in size, was first described in gastrointestinal stromal tumor cells.…”