Abstract
Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Through exosomes, mesenchymal stem cells confer chemoresistance to MM cells, while myeloma cells promote angiogenesis, influence immune response, cause bone lesions, and have an impact on the outcome of MM patients. In this review, we analyze the role played by exosomes in the progression of monoclonal gammopathies and the effects on the proliferation of neoplastic plasma cells, and discuss the possible employment of exosomes as potential targets for the treatment of MM patients.
Highlights
Overview of ExosomesThe intercellular interactions between hematological tumors and the bone marrow (BM) milieu are due to soluble components and to cell-to-cell connections
These results demonstrate that serglycin has a relevant effect in supporting the protein cargo in MM-originated exosomes and proposes that targeting serglycin may modify the effect of these exosomes on MM progression [115]
Via the discharge of exosomes, tumor cells interrelate with a huge number of cells, comprising cells of the tumor BM milieu that enhance disease progress by causing a reduction of immune response and provoking drug resistance
Summary
The intercellular interactions between hematological tumors and the bone marrow (BM) milieu are due to soluble components and to cell-to-cell connections. Proteins of exosomes comprise costimulatory molecules such as CD86, antigen presenting proteins such as MHC-I and MHC-II, membrane fusion proteins such as annexins, intercellular adhesion molecule 1, integrins, tetraspanins, multivesicular body formation proteins such as Alix and Tsg, and transmembrane molecules. These proteins are plentiful on the surfaces of exosomes, while other substances such as cytoskeleton proteins, heat shock proteins, and several types of enzymes such as glucose 6 and pyruvate kinase are present inside exosomes [3]. RNA is placed in the endoplasmic reticulum in which it exercises its effects, while vacant EVs combine with lysosomes for degradation [11]
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