Extracellular vesicle cross-talk in the bone marrow microenvironment: implications in multiple myeloma

Abstract

The bone marrow (BM) represents a complex microenvironment containing stromal cells, immune cells, osteoclasts, osteoblasts, and hematopoietic cells, which are crucial for the immune response, bone formation, and hematopoiesis. Apart from soluble factors and direct cell-cell contact, extracellular vesicles (EVs), including exosomes, were recently identified as a third mediator for cell communication. Solid evidence has already demonstrated the involvement of various BM-derived cells and soluble factors in the regulation of multiple biological processes whereas the EV-mediated message delivery system from the BM has just been explored in recent decades. These EVs not only perform physiological functions but can also play a role in cancer development, including in Multiple Myeloma (MM) which is a plasma cell malignancy predominantly localized in the BM. This review will therefore focus on the multiple functions of EVs derived from BM cells, the manipulation of the BM by cancer-derived EVs, and the role of BM EVs in MM progression.

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

“…Exosomes are generated from endosomal origins constitutively, released by various cells, and more frequently by tumor cells [6][7][8]. Exosomes are actively secreted from cells by an exocytosis pathway used for receptor removal and crosstalk between cells.…”

“…Exosomes are actively secreted from cells by an exocytosis pathway used for receptor removal and crosstalk between cells. Exosomes contain many important components such as proteins, RNA, DNA, and lipids for cancer-stromal communication [8][9]. Specifically, cell-secreted microRNAs (miRNAs) with the length of 18-22 nucleotides are predominantly carried by exosomes [10].…”

Chemical and thyroid hormone profile of the bone marrow interstitial fluid in hematologic disorders and patients without primary hematologic disorders

“…The interstitial fluid, which encompasses the extracellular fluid surrounding cells within a specific tissue, has emerged as a major component of the tumor microenvironment. In the bone marrow, the interstitial fluid serves as an important niche containing soluble secretory factors that are present between bone marrow cells . Several studies have specifically examined the composition of the interstitial fluid within the bone marrow.…”

“…Transmission of several key signaling molecules such as IL‐6 and IL‐8 within the interstitial compartment serves a major function in chemotaxis and hematopoiesis . In addition, extracellular vesicles secreted into the interstitial compartment are associated with effects on the immune response, cell migration, and differentiation and angiogenesis and were demonstrated to enhance growth of hematologic malignancies such as multiple myeloma (MM) …”

Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

“…Exosomes, secreted from living cells, have been used as nanometric vehicles for therapeutic drug and gene delivery. They are biocompatible, non-cytotoxic, low immunogenic, simple to produce, easy to store, have a long life span, and high cargo loading capacity (Munagala et al, 2016; Srivastava et al, 2016; Wang et al, 2016b). These characteristics make exosomes a promising drug carrier for cancer treatment (Tian et al, 2013; Tang et al, 2015; Pitt et al, 2016).…”