Bone marrow stromal cell interaction reduces Syndecan-1 expression and induces kinomic changes in myeloma cells

Fuhler, Gwenny M.; Baanstra, Mirjam; Chesik, Daniel; Somasundaram, Rajesh; Seckinger, Anja; Hose, Dirk; Peppelenbosch, Maikel P.; Bos, Nicolaas

doi:10.1016/j.yexcr.2010.03.013

Cited by 39 publications

(38 citation statements)

References 54 publications

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“…[8][9][10] The tumor BM microenvironment also supports tumor growth, 11 induces chemoresistance, and selects for tumor-initiating clones. 12 Therefore, a realistic model of the abnormal BM seen in MM patients would greatly benefit translational research scientists.…”

Section: Introductionmentioning

confidence: 99%

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

Reagan

Mishima

Glavey

et al. 2014

Blood

112

134

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Key Points• 3D bone marrow niche model recapitulates in vivo interactions of tumor and bone cells in a more biologically relevant system than in 2D.• Differential expression levels of miRs in MSCs provide novel insights into mechanisms of regulation of osteoblasts in multiple myeloma.Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required.Herein we have developed a clinically relevant, three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The coculture model and clinical samples were used to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillarylike assembly of endothelial cells and cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor (ND)-and MM-MSC miRNA (miR) signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically relevant tool to model cancer growth within the bone-useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel bone anabolic miRs in MM opens more opportunities for novel approaches to cancer therapy via stromal miR modulation. (Blood. 2014;124(22):3250-3259)

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Section: Introductionmentioning

confidence: 99%

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

Reagan

Mishima

Glavey

et al. 2014

Blood

112

134

View full text Add to dashboard Cite

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“…Interestingly, recent studies suggest that CD138 expression on myeloma cells may be reversible and is dependent on the microenvironment (9). Thus, the significance of CD138 expression needs to be carefully interpreted and for precise characterization of myeloma stem cells further qualities have to be considered.…”

Section: Introductionmentioning

confidence: 99%

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

Morgenroth

Vogg

Zlatopolskiy

et al. 2014

Molecular Cancer Therapeutics

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“…The significance of CD138 expression on clonogenic MM cells thus needs to be carefully interpreted. It was reported that interaction with bone marrow stromal cells induced expression of CD138 in MM plasma cells, 26 suggesting that changes in CD138 expression depend on the microenvironment. In addition, 15 In addition, since clonogenic MM plasma cells mainly reside in the BM microenvironment, it is also important to understand the mechanisms involved in how the BM microenvironment supports clonogenic MM plasma cells and targets them.…”

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confidence: 99%

CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients

et al. 2012

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Bone marrow stromal cell interaction reduces Syndecan-1 expression and induces kinomic changes in myeloma cells

Cited by 39 publications

References 54 publications

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients

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