Communication between bone marrow mesenchymal stem cells and multiple myeloma cells: Impact on disease progression

Abstract

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow (BM). The interaction between MM cells and the BM microenvironment, and specifically BM mesenchymal stem cells (BM-MSCs), has a key role in the pathophysiology of this disease. Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs, aiding the progression of this hematological tumor. The relation of MM cells with the resident BM-MSCs is a two-way interaction. MM modulate the behavior of BM-MSCs altering their expression profile, proliferation rate, osteogenic potential, and expression of senescence markers. In turn, modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression. The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs, long non-coding RNAs or other molecules. However, the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes. Thus, understanding the way this communication works and developing strategies to interfere in the process, would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.

Keywords: Multiple myeloma; Mesenchymal stem cells; Bone marrow microenvironment; Soluble factors; Extra-cellular vesicles; Cells adhesion molecules; Tunnelling-nanotubes

Core Tip: Mesenchymal stem cells (MSCs), the main cell population of the bone marrow (BM) stroma, can influence BM microenvironment through their paracrine activity, involving both soluble factors and extracellular vesicles, but also through direct communication. Being the BM the predominant localization of multiple myeloma cells (MM), finding the appropriate conditions at this niche, is key for the survival and expansion of tumour cells and thus, for the progression of the disease. Since the activity of BM-MSCs could determine the fate of MM cells at BM, these cells could be interesting targets for the design of new antitumor drugs.