Abstract
Extracellular vesicles (EVs) are a heterogeneous group of particles, between 15 nanometers and 10 microns in diameter, released by almost all cell types in physiological and pathological conditions, including tumors. EVs have recently emerged as particularly interesting informative vehicles, so that they could be considered a true “cell biopsy”. Indeed, EV cargo, including proteins, lipids, and nucleic acids, generally reflects the nature and status of the origin cells. In some cases, EVs are enriched of peculiar molecular cargo, thus suggesting at least a degree of specific cellular packaging. EVs are identified as important and critical players in intercellular communications in short and long distance interplays. Here, we examine the physiological role of EVs and their activity in cross-talk between bone marrow microenvironment and neoplastic cells in hematological malignancies (HMs). In these diseases, HM EVs can modify tumor and bone marrow microenvironment, making the latter “stronger” in supporting malignancy, inducing drug resistance, and suppressing the immune system. Moreover, EVs are abundant in biologic fluids and protect their molecular cargo against degradation. For these and other “natural” characteristics, EVs could be potential biomarkers in a context of HM liquid biopsy and therapeutic tools. These aspects will be also analyzed in this review.
Highlights
Extracellular vesicles (EVs), a heterogeneous group of lipid bilayer particles between 15 nanometers and 10 microns in size, are released by almost all cell types [1]
chronic myeloid leukemia (CML)-derived Exo promoted the proliferation and survival of CML cells, both in vitro and in vivo, by TGF-β1/TGF-β1 receptor engagement [77]. This EV autocrine loop did not work in a chronic lymphocytic leukemia (CLL) model [71]; a possible explanation could be that CLL cells did not express heparan sulphate (HS) receptors required for the EV uptake [78]
We have previously reported that serum MV count in CLL, non-Hodgkin’s lymphoma (NHL), Waldenstrom’s macroglobulinemia (WM), Hodgkin lymphoma (HL), MM, acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndrome (MDS) patients are high compared to healthy subjects [36]
Summary
Extracellular vesicles (EVs), a heterogeneous group of lipid bilayer particles between 15 nanometers and 10 microns in size, are released by almost all (normal and neoplastic) cell types [1]. EVs play important roles in intercellular cross-talk in both short and long distances [1,52]; they are involved in numerous physiological processes, including stem cell renewal and differentiation [53], tissue repair [31], immune surveillance [33], and blood coagulation [33,54]. For these reasons, they have been highly preserved through evolution [9,18]. They enhance EVs ainntgeiroagcetnwesiitsh, einxhtribaicteltlhuelairmmmautnriexstyosptermom, aontedtuinmduocreinavasusipopnr.esMsioorneoovf ehr,emthaetyopenoiheatinccseteamngaiongdenesis, inhibpirtogtheneitiomr mceulln(eHsSyPsCt)emfu,nactniodnsinadnudcea astesmupcperlles(SsiCo)nmoaflihgenmanatttorpanosifeotricmasttieomn. aMnMd Pp9r:oMgeantriitxor cell (HSPmCe)taflulonpcetpiotindsasaend; a IsLt6e:mincteelrlle(uSkCi)nema6l;igMnaDnStCt:raMnsyfeolormid atDioenri.veMd MSPu9p:prMesastorrixCmelelst;allMopSCeps:tidase 9; ILm6:eisnetnecrhlyemukailnsete6m; /MstrDomSCal: cMelylse;lNoiKd: DnaetruirvaeldkiSlluerpcperlless.sor Cells; MSCs: mesenchymal stem/stromal cells; NK: natural killer cells
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