Differential expression of bone marrow derived mesenchymal stem cells in patients with multiple myeloma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196321 | GEO | 2022/03/23
REPOSITORIES: GEO
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Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.
2018-07-14 | GSE108915 | GEO
Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.
2018-06-08 | GSE110271 | GEO
Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is a refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.
2018-06-08 | GSE110238 | GEO
Project description:Multiple myeloma (MM) is a hematological cancer with inevitable drug resistance. MM cells interacting with bone marrow stromal cells (BMSCs) undergo substantial changes in transcriptome and develop de novo drug resistance. As a critical component in transcriptional regulation, how chromatin landscape is transformed in MM cells and regulates the transcriptional response to BMSCs remains elusive. We profiled transcriptome and regulome for MM cells using a transwell coculture system with BMSCs. The transcriptome and regulome of MM cells from the upper transwell resembled MM cells coexisting with BMSCs from the lower chamber but were distinctive to monoculture. BMSC-induced genes were enriched in JAK2/STAT3 signaling pathway, unfolded protein stress, signatures of early plasma cells, and response to proteasome inhibitors. Genes with accessibility increased at multiple regulatory sites were preferentially induced by BMSCs and enriched in response to drug and unfavorable prognostic markers from several MM patient cohorts. We proposed JUNB and ATF4::CEBPβ as candidate transcription factors (TFs) that modulated the BMSC-induced transformation of regulome linked to the response to external stimuli. Together, we characterized BMSC-induced transcriptome and regulome signatures of MM cells and prioritized TFs for future study to depict epigenetic mechanisms of BMSC-induced drug resistance in MM.
2022-02-16 | GSE193657 | GEO
Project description:Multiple myeloma (MM) is a hematological cancer with inevitable drug resistance. MM cells interacting with bone marrow stromal cells (BMSCs) undergo substantial changes in transcriptome and develop de novo drug resistance. As a critical component in transcriptional regulation, how chromatin landscape is transformed in MM cells and regulates the transcriptional response to BMSCs remains elusive. We profiled transcriptome and regulome for MM cells using a transwell coculture system with BMSCs. The transcriptome and regulome of MM cells from the upper transwell resembled MM cells coexisting with BMSCs from the lower chamber but were distinctive to monoculture. BMSC-induced genes were enriched in JAK2/STAT3 signaling pathway, unfolded protein stress, signatures of early plasma cells, and response to proteasome inhibitors. Genes with accessibility increased at multiple regulatory sites were preferentially induced by BMSCs and enriched in response to drug and unfavorable prognostic markers from several MM patient cohorts. We proposed JUNB and ATF4::CEBPβ as candidate transcription factors (TFs) that modulated the BMSC-induced transformation of regulome linked to the response to external stimuli. Together, we characterized BMSC-induced transcriptome and regulome signatures of MM cells and prioritized TFs for future study to depict epigenetic mechanisms of BMSC-induced drug resistance in MM.
2022-02-16 | GSE193656 | GEO
Project description:In multiple myeloma (MM), abnormal plasma cells interact with bone marrow (BM) stromal cells and vascular cells among others. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that extracellular vesicles (EVs)-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the EVs and EV-miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread. We found that the MM-BMSC-EVs enhanced the cell proliferation of RPMI8226. The EV-miRNA expression was different between MM-BMSCs and Normal-BMSCs, and some miRNAs, including miR-10a, were significantly up-regulated in the MM-BMSC-EVs. We then visualized with an in vitro model the uptake of Cy3-labeled miR-10a into RPMI8226 via EVs. To identify the function of miR-10a in MM cells, miR-10a mimic was transfected into RPMI8226 cells.
2018-09-30 | GSE118282 | GEO
Project description:The aging of bone marrow stromal cells (BMSCs) lead to decreased ability to maintain hematopoiesis, however, effects of aging on BMSC-derived exosomes in bone marrow microenvironment remain unclear. The aim of this study is therefore to determine the age-related change of BMSC-derived exosomal miRNAs. Human BMSCs of young (yBMSC s, age of donors: 19 and 20 years) and elderly (eBMSC s, age of donors: 68 and 72 years) donors were purchased from Lonza. BM samples were obtained from MM patients (age of donors: 62 and 77 years) in accordance with the Declaration of Helsinki and using protocols approved by the research Ethics Committee of Tokyo Medical University (IRB No. 2648), and BMSCs derived from MM patients (mmBMSCs) were isolated using the classical plastic adhesion method. The exosomes from culture medium of BM-MSCs were isolated by Total Exosome Isolation Reagent (Invitrogen). Exosomal miRNA profiling was done using a TaqMan low-density array (ABI), and Studentâ??s t-test was used to determine statistical significance for comparisons between young and old groups using R software.
2017-05-12 | E-GEOD-78865 | biostudies-arrayexpress
Project description:Bone marrow (BM) microenvironment of multiple myeloma (MM) is populated by tumor associated monocytes and macrophages (TAMs), where they protect clonal plasma cells (PC). It is well known that MM cells can modulate the transcriptome of macrophages, thus, we sought to investigate if a key component of the tumor microenvironment such as MM-BMSCs have the potential to modulate the transcriptome of macrophages as MM cells do. We used microarrays to analyze the potential of MM-BMSC to polarize the transcriptome of TAMs in the presence and absence of MM cells
2023-11-05 | GSE122160 | GEO
Project description:miRNA expression profiling was performed on MM.1S MM cells cultured 8 hours in control media or 50nM RGB-286638, with or without BMSCs. The emerging role of miRNAs in the pathogenesis of multiple myeloma (MM) led us to hypothesize that the miRNA network might be among the inducible transcriptional alterations consequent to MM-bone marrow stromal cell (BMSC) interactions. Our data suggests that BMSC induced MM transcription led to aberrant miRNA expression. We therefore hypothesized that agents interfering with RNAPII transcription might inhibit aberrant miRNA expression in MM. To test this hypothesis we used RGB-286638, a novel protein kinase inhibitor, which works primarily via RNAPII inhibition followed by transcriptional arrest in MM cells. miRNA profiling of RGB-286638-exposed MM cells resulted in RNAPII arrest associated with reduced miRNA levels. RGB-286638 abrogated BMSCs-induced miRNAs, which correlated with growth arrest in MM cells. Analysis of RGB-286638-induced differentially-expressed miRNAs in MM cells, in the presence or absence of BMSCs, revealed RNAPII regulation of expression of BMSC-inducible miRNAs with established oncogenic functions in MM Our findings demonstrate the role of RNAPII in regulating miRNA network, suggesting a new rationale for using agents interfering with RNAPII transcription in the treatment of MM.
2012-06-01 | GSE38364 | GEO
Project description:Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of mesenchymal stem cells (MSCs). Stromal communication with cancer cells can influence treatment response. Understanding the cellular interactions within the tumor-bone milieu is critical to the development of novel agents that can reverse bone diseases. Here we identified that bioactive lncRNA RUNX2-AS1 in myeloma cells could be incorporated into exosomes and transmitted to MSCs, thus repressing the osteogenesis of MSCs. RUNX2-AS1, which arises from the antisense strand of RUNX2, was enriched in MSCs derived from MM patients (MM-MSCs). RUNX2-AS1 was capable of forming an RNA duplex with RUNX2 pre-mRNA at overlapping regions and this duplex transcriptionally repressed RUNX2 expression by reducing the splicing efficiency, resulting in decreased osteogenic potential of MSCs. In vivo mouse models, intraperitoneally administered GW4869, an inhibitor of exosome secretion, was found to be effective in prevention of bone loss, sustained by both bone-forming and anticatabolic activities. Therefore, exosomic lncRNA RUNX2-AS1 may serve as a potential therapeutic target for bone lesions in MM. In summary, our results indicated a unique role of exosomic lncRUNX2-AS1 in transferring from MM cells to MSCs in osteogenic differentiation, through a novel exosomic lncRUNX2-AS1/RUNX2 signaling pathway.
2020-12-15 | GSE108159 | GEO