Chemotherapy Promotes Release of Exosomes Which Upregulate Cholesterol Synthesis and Chemoresistance in AML Blasts.

Abstract

Extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication as well as a major mechanism of functional reprogramming of cells in disease [1-2]. All cells produce EVs, which freely circulate and are found in all body fluids. EVs are heterogenous, consisting of subsets of vesicles with different sizes, distinct origins, and various functions (Figure 1). They mediate a broad variety of biological events ranging from cellular activation, inflammation, blood coagulation, angiogenesis, cellular transport, and others. Among these vesicles, a subset of small EVs (30-150 nm in diameter) originating from multivesicular bodies (MVBs) in parent cells and referred to as small extracellular vesicles (sEVs) carry proteomic, genomic and functional signatures that resemble those of parent cells and are, therefore, taken as surrogates of parent cells. In cancer, tumor-derived exosomes (TEX) reflect characteristics of tumor cells and are considered candidates for “liquid tumor biopsy” [3]. Emerging evidence shows that TEX are a major sEV subset in plasma of patients with cancer, including hematologic malignancies [4].