Abstract
Multiple myeloma (MM), the second most common hematological malignancy, is an incurable cancer of plasma cells. MM cells diffusely involves the bone marrow (BM) and establish a close interaction with the BM niche that in turn supports MM survival, proliferation, dissemination and drug resistance. In spite of remarkable progress in understanding MM biology and developing drugs targeting MM in the context of the BM niche, acquisition of multi-class drug resistance is almost universally inevitable. Exosomes are small, secreted vesicles that have been shown to mediate bidirectional transfer of proteins, lipids, and nucleic acids between BM microenvironment and MM, supporting MM pathogenesis by promoting angiogenesis, osteolysis, and drug resistance. Exosome content has been shown to differ between MM patients and healthy donors and could potentially serve as both cancer biomarker and target for novel therapies. Furthermore, the natural nanostructure and modifiable surface properties of exosomes make them good candidates for drug delivery or novel immunomodulatory therapy. In this review we will discuss the current knowledge regarding exosome’s role in MM pathogenesis and its potential role as a novel biomarker and therapeutic tool in MM.
Highlights
Multiple myeloma is the second most common hematological malignancy in the Western world after non-Hodgkin lymphoma, accounting for approximately 13% of all hematological cancers [1]
The facts that the primary oncogenic mutations observed in MM patients are already present in monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) and that genomic landscape appears remarkably similar across the plasma cell disorder spectrum, suggest that the bone marrow (BM) microenvironment may play a crucial role in disease progression from an asymptomatic state to malignant neoplasms [8, 9]
An in vitro study showed that bone marrow stromal cells (BMSCs)-derived exosomes induced the survival and expansion of myeloid-derived suppressor cell (MDSC) through activating signal transducer and activator of transcription (STAT) 3 and STAT1 pathways and increasing the anti-apoptotic proteins B-cell lymphoma-extra large (Bcl-xL) and induced myeloid leukemia cell differentiation protein Mcl-1 [29]
Summary
Multiple myeloma is the second most common hematological malignancy in the Western world after non-Hodgkin lymphoma, accounting for approximately 13% of all hematological cancers [1]. The facts that the primary oncogenic mutations observed in MM patients are already present in MGUS or SMM and that genomic landscape appears remarkably similar across the plasma cell disorder spectrum, suggest that the BM microenvironment may play a crucial role in disease progression from an asymptomatic state to malignant neoplasms [8, 9]. Exosomes are small (30-100nm diameter) membrane vesicles generated in multivesicular endosomes (MVEs) and released upon the fusion of MVEs with cell membrane [11, 12] These nano vesicles are secreted by most cell types under both physiological and pathological conditions, mediating local and systemic cell-to-cell communication through selective transfer of mRNA, non-coding RNA (ncRNA), proteins, and lipids [13, 14]. There is a growing interest in understanding how exosomes contribute to MM pathogenesis and if they could be use as a therapeutic vehicle in MM treatment
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