MicroRNA expression changes in Bone Marrow Stromal Cells from Myeloma Patients vs Normal Patients, and From Normal Patients cultured with or without Myeloma cells in 3D culture
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE60423 | GEO | 2014/11/01
SECONDARY ACCESSION(S): PRJNA258217
REPOSITORIES: GEO
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Project description:The objectives of this study were to assess differences in Bone Marrow Derived Menenchymal Stromal Cells (MSCs) during co-culture with myeloma cells, and to assess differences in myeloma patient MSCs compared to normal donor MSCs. In the study presented here, a Bone Marrow Derived Menenchymal Stromal Cells (MSCs) were analyzed after FACS sorting from 2 week culture in osteogenic media lacking dexamethasone in 3D silk scaffold matrices either in co-culture with the multiple myeloma cell line GFP+Luc+MM1.S or Alone, as controls. Also, monocultures of MSCs grown in 2D, in MSC expansion media, from Normal Donor Controls (ND) or Multiple myeloma patients (MM) were analyzed. Analysis was done looking at microRNA expression in samples with the nanoString microRNA platform for 800 microRNAs.
2014-11-01 | E-GEOD-60423 | biostudies-arrayexpress
Project description:It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,M-bM-^@M-&) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1M-NM-2 and TNF-M-NM-1 as compared with normal BM-MSCs. In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs. BM-MSCs were isolated from 3 healthy donors and 4 untreated multiple myeloma patients. Total RNA from BM-MSCs was exctracted and hybridyzed on Affymetrix GeneChipM-BM-. Human Genome U133 Plus 2.0 Array. Amplification, hybridization and scanning were done according to standard Affymetrix protocols (www.affymetrix.com). CEL files were normalized with RMA method.
2013-03-21 | E-GEOD-36474 | biostudies-arrayexpress
Project description:Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs).
2022-03-23 | GSE196321 | GEO
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of primary multiple myeloma plasma cells (MMPCs) and mesenchymal stem cells (MSCs) before and after co-culture was done using Affymetrix microarrays. Thirteen MMPC and MSC co-culture experiments using MMPCs from 8 patients and MSCs from 5 healthy donors were performed.
2015-08-13 | E-GEOD-31159 | biostudies-arrayexpress
Project description:Mesenchymal stromal cells (MSCs) derived from the BM of healthy donors (dMSCs) and myeloma patients (pMSCs) were co-cultured with the model myeloma cell line - MM.1S -, and the gene expression profile of MSCs induced by this interaction was analyzed using high density oligonucleotide microarrays. Deregulated genes in co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and inhibition of osteoblasts. Additional genes induced by co-culture were exclusively deregulated in pMSCs and were predominantly associated to RNA processing, the ubiquitine-proteasome pathway, regulation of cell cycle and Wnt signaling. Primary MSCs from bone marrow (BM) samples of healthy donors (n=8) and multiple myeloma (MM) patients (n=13) were generated as described by Garayoa et al. 2009 (PMID:19357701). Ficoll-Paque density gradient separation medium was used to isolate mononuclear cells from BM aspirates. MSCs were selected by adherence to plastic and subsequently expanded until passage 2 when they were used for co-culture. For the MSC-MM.1S co-cultures we used a 6-well format transwell system with 1 M-BM-5m pore size membrane. Briefly, 2 X 10^4 MSCs were first cultured attached to the lower side of the membrane, and when reached M-bM-^IM-^H 85% confluence 1 X 10^6 MM.1S cells were seeded on the upper side. After 24 h co-culture in RPMI 1640 medium supplemented with 10% FBS and antibiotics, MSCs were recovered by trypsinization, washed once in PBS and stored at -80M-BM-0C in RLT buffer (Qiagen) until RNA extraction. Absence of MM.1S cells in the recovered MSC population was assessed in selected samples by flow cytometry analysis.
2014-11-23 | E-GEOD-46053 | biostudies-arrayexpress
Project description:Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically delivered locked nucleic acid (LNA)-modified anti-miR-138 oligonucleotides in suppressing myeloma bone disease. We showed that expression of miR-138 was significantly increased in MSCs from MM patients (MM-MSCs) and myeloma cells compared to those from healthy subjects. Furthermore, inhibition of miR-138 resulted in enhanced osteogenic differentiation of MM-MSCs in vitro and increased number of endosteal osteoblastic lineage cells (OBCs) and bone formation rate in mouse models of myeloma bone disease. RNA sequencing of the OBCs identified TRPS1 and SULF2 as potential miR-138 targets that were de-repressed in anti-miR-138 treated mice. In summary, these data indicate that inhibition of miR-138 enhances bone formation in MM and that pharmacological inhibition of miR-138 could represent a new therapeutic strategy for treatment of myeloma bone disease.
2018-06-01 | GSE111651 | GEO
Project description:To explore the possible differences in gene expression profiles between MSCs cultured alone and MSCs in leukemia niches
2023-09-13 | GSE212209 | GEO
Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.
2023-01-04 | PXD032753 | Pride
Project description:Mesenchymal stem/stromal cells (MSCs) derived from the BM of healthy donors (dMSCs) and myeloma patients (pMSCs) were co-cultured with the model myeloma cell line - MM.1S -, and the gene expression profile of MSCs induced by this interaction was analyzed using high density oligonucleotide microarrays. Deregulated genes in co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and inhibition of osteoblasts. Additional genes induced by co-culture were exclusively deregulated in pMSCs and were predominantly associated to RNA processing, the ubiquitine-proteasome pathway, regulation of cell cycle and Wnt signaling.
2014-11-23 | GSE46053 | GEO
Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>
2022-04-27 | MTBLS676 | MetaboLights