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Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma
Review

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

1
University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria, 39008 Santander, Spain
2
Cancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Taketo Yamada
Cancers 2021, 13(11), 2542; https://doi.org/10.3390/cancers13112542
Received: 24 April 2021 / Revised: 16 May 2021 / Accepted: 19 May 2021 / Published: 22 May 2021
(This article belongs to the Special Issue Tumor Microenvironment and Exacerbation Mechanism in Multiple Myeloma)
Multiple myeloma is a cancer of immunoglobulin-secreting cells that accumulate in the bone marrow. Mesenchymal stromal cells are important components of the bone marrow microenvironment interacting with myeloma cells and having a pivotal role in the progression of the disease. Here we first review studies that have highlighted structural and functional differences between mesenchymal stromal cells derived from healthy donors and myeloma patients, and propose a model for the transition from the normal to the myeloma-condition of these cells. Next, we underscore the contribution of mesenchymal stromal cells to the promotion of myeloma growth and survival, development of drug resistance, dissemination and homing, myeloma bone disease, and the establishment of a pro-inflammatory and immunosuppressive microenvironment. It appears as if as a result of myeloma-mesenchymal stromal cell cross-talk, mesenchymal stromal cells in myeloma patients have converted into active contributors to the pathophysiology of the disease.
Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment. View Full-Text
Keywords: multiple myeloma; bone marrow mesenchymal stromal cells; myeloma progression multiple myeloma; bone marrow mesenchymal stromal cells; myeloma progression
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MDPI and ACS Style

Maiso, P.; Mogollón, P.; Ocio, E.M.; Garayoa, M. Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression. Cancers 2021, 13, 2542. https://doi.org/10.3390/cancers13112542

AMA Style

Maiso P, Mogollón P, Ocio EM, Garayoa M. Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression. Cancers. 2021; 13(11):2542. https://doi.org/10.3390/cancers13112542

Chicago/Turabian Style

Maiso, Patricia, Pedro Mogollón, Enrique M. Ocio, and Mercedes Garayoa. 2021. "Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression" Cancers 13, no. 11: 2542. https://doi.org/10.3390/cancers13112542

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