Mesenchymal stem cells in multiple myeloma: a therapeutical tool or target?

Xu, Song; Veirman, Kim De; Becker, Ann De; Vanderkerken, Karin; Riet, Ivan Van

doi:10.1038/s41375-018-0061-9

Cited by 88 publications

(77 citation statements)

References 114 publications

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“…Most studies on MSCs in MM have used cultures of expanded MSCs or MSC lines in in vitro and in vivo models (Xu et al, 2018). The profiles of gene expression (Corre et al, 2007;Garcia-Gomez et al, 2014), proteins (Slany et al, 2014) and microRNA (Reagan et al, 2014;Berenstein et al, 2015) of cultured MSCs generated from MM patients differ from those of healthy donors.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

et al. 2018

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Summary Recent studies suggest that multiple myeloma (MM) induces proliferation and expansion of bone marrow (BM) mesenchymal stem cells (MSCs), but others showed that MM cells induce MSC senescence. To clarify the interaction between MM and MSCs, we exploited our established MSC gene signature to identify gene expression changes in myeloma MSCs and associated functional differences. Single MSCs from patients with MM had changes in expression of genes associated with cellular proliferation and senescence and a higher proportion of senescent cells and lower proliferative potential than those from age‐matched healthy donors. Single MSCs from both sources heterogeneously express MSC genes associated with adipogenesis and osteoblastogenesis. We identified the gene encoding insulin‐like growth factor‐binding protein 2 (IGFBP2), an MSC gene commonly altered in high risk MM, as under‐expressed. Morphologically, IGFBP2+ cells are underrepresented in MM BM compared to smouldering MM. Strong IGFBP2 and adiponectin co‐expression was detected in a subset of small adipocytes. Co‐culturing normal MSCs with myeloma cells suppressed MSC differentiation to adipocytes and osteoblasts, and reduced expression of IGFBP2 and adiponectin. Recombinant IGFBP2 blocked IGF1‐mediated myeloma cell growth. Our data demonstrate that myeloma MSCs are less proliferative and that IGFBP2+ small adipocytes are a distinct mesenchymal cell population suppressed by myeloma.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

et al. 2018

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“…Mesenchymal stem cells, of unclear origin in MM [31], represent an important component of the "vascular and osteoblast niche" [31][32][33]. They are potentially able to differentiate into multiple histotypes (i.e., fibroblasts, adipocytes, chondrocytes, and osteoblasts) and can migrate towards tumor sites modulating MM growth and playing a critical role in disease outcome [31,33]. There is evidence of mesenchymal stem cells-induction of bortezomib resistance in MM plasma cells by increasing Bcl2 expression and enhancing NF-κB activity via cell-cell contact [34,35].…”

Section: The "Vascular Niche"mentioning

confidence: 99%

Bone Marrow Stromal Cells-Induced Drug Resistance in Multiple Myeloma

Ria

Vacca

2020

IJMS

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Multiple myeloma is a B-cell lineage cancer in which neoplastic plasma cells expand in the bone marrow and pathophysiological interactions with components of microenvironment influence many biological aspects of the malignant phenotype, including apoptosis, survival, proliferation, and invasion. Despite the therapeutic progress achieved in the last two decades with the introduction of a more effective and safe new class of drugs (i.e., immunomodulators, proteasome inhibitors, monoclonal antibodies), there is improvement in patient survival, and multiple myeloma (MM) remains a non-curable disease. The bone marrow microenvironment is a complex structure composed of cells, extracellular matrix (ECM) proteins, and cytokines, in which tumor plasma cells home and expand. The role of the bone marrow (BM) microenvironment is fundamental during MM disease progression because modification induced by tumor plasma cells is crucial for composing a “permissive” environment that supports MM plasma cells proliferation, migration, survival, and drug resistance. The “activated phenotype” of the microenvironment of multiple myeloma is functional to plasma cell proliferation and spreading and to plasma cell drug resistance. Plasma cell drug resistance induced by bone marrow stromal cells is mediated by stress-managing pathways, autophagy, transcriptional rewiring, and non-coding RNAs dysregulation. These processes represent novel targets for the ever-increasing anti-MM therapeutic armamentarium.

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“…Mesenchymal stem cells (MSCs) are the major component of BM stroma [11,57,[70][71][72]. These cells, of unclear origin in MM [71], are potentially able to differentiate into multiple histotypes (i.e.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…These cells, of unclear origin in MM [71], are potentially able to differentiate into multiple histotypes (i.e. fibroblasts, adipocytes, chondrocytes, and osteoblasts) and in the BM form specialized niches namely "vascular niche" and "osteoblast niche" [57,70,71]. MSCs support tumor cell growth, metastasis, survival, bone marrow colonization, and evasion of the immune system [72].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Angiogenesis and Antiangiogenesis in Multiple Myeloma

Ria¹,

Solimando²,

Melaccio³

et al. 2019

Update on Multiple Myeloma

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Multiple myeloma progression is characterized by a dense interaction between cancer cells and bone marrow microenvironment. The interactions of myeloma cells with various stromal cells and extracellular matrix components are the main regulator of the biological processes that underlie the progression of the disease and of the classic symptomatology correlated. The bone marrow of myeloma patients has recognized autocrine and paracrine loops that regulate multiple signaling pathways and the malignant phenotype of plasma cells. One of the pivotal biological processes which are responsible for myeloma progression is the formation of new vessels from existing ones, known as angiogenesis. It represents a constant hallmark of disease progression and a characteristic feature of the active phase of the disease. Near angiogenesis, other two ancestral processes were active in the bone marrow: vasculogenesis and vasculogenic mimicry. These processes are mediated by the angiogenic cytokines, interleukins, and inflammatory cytokines directly secreted by plasma cells and stromal cells. Neovascularization is also mediated by direct interaction between plasma cells and the various components of bone marrow microenvironment. The observation of the increased bone marrow angiogenesis in multiple myeloma and its correlation with disease activity and overall survival led to consider angiogenesis as a new target in the treatment of multiple myeloma.

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Mesenchymal stem cells in multiple myeloma: a therapeutical tool or target?

Cited by 88 publications

References 114 publications

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

Bone Marrow Stromal Cells-Induced Drug Resistance in Multiple Myeloma

Angiogenesis and Antiangiogenesis in Multiple Myeloma

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