Breast cancer hybrid cells after spontaneous cell fusion with MSC display tumor dorming-like properties
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PROVIDER: PRJNA660432 | ENA |
REPOSITORIES: ENA
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Project description:Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation in co-cultures of primary human mesenchymal stroma/stem-like cells (MSC) with human MDA-MB-231 breast cancer cells. Lentiviral fluorescence-labeled MSC with eGFP and breast cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells. Double FACS sorting and single cell cloning revealed different aneuploid hybrid populations (MDA-hyb1 MDA-hyb3, MDA-hyb5)
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2018-10-29 | GSE117411 | GEO
Project description:Transcriptional properties of estrogen receptor fusion genes.
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Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.
2019-03-26 | PXD012768 | Pride
Project description:Mesenchymal stromal cells (MSC) are ideal candidates for cell therapies, due to their immune-regulatory and regenerative properties. We have previously reported that lung-derived MSC are tissue-resident cells with lung-specific properties compared to bone marrow-derived MSC. Assessing relevant molecular differences between lung-MSC and bone marrow-MSC is important, given that such differences may impact their behavior and potential therapeutic use. Here, we present an in-depth mass spectrometry (MS) based strategy to investigate the proteomes of lung-MSC and bone marrow-MSC. The MS-strategy relies on label free quantitative data-independent acquisition (DIA) analysis and targeted data analysis using a MSC specific spectral library. We identified several significantly differentially expressed proteins between lung-MSC and bone marrow-MSC within the cell layer (352 proteins) and in the conditioned medium (49 proteins). Bioinformatics analysis revealed differences in regulation of cell proliferation, which was functionally confirmed by decreasing proliferation rate through Cytochrome P450 stimulation. Our study reveals important tissue-specific differences within proteome and matrisome profiles between lung- and bone marrow-derived MSC that may influence their behavior and affect the clinical outcome when used for cell-therapy.
2018-10-18 | PXD006419 | Pride
Project description:Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation in co-cultures of primary human mesenchymal stroma/stem-like cells (MSC) with human MDA-MB-231 breast cancer cells. Lentiviral fluorescence-labeled MSC with eGFP and breast cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells. Double FACS sorting and single cell cloning revealed two different aneuploid male hybrid populations (MDA-hyb1 and MDA-hyb2)
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Project description:Aims. We sought to analyze the physiological differences of human C-MSC between the left ventricle (LV) versus the right ventricle (RV) . Methods and results. Autoptic cardiac specimens from LV and RV were obtained from healthy donors. Part was used for tissue sections; part was processed to obtain C-MSC. Isogenic LV and RV C-MSC were compared as for surface markers expression, cell proliferation/death ratio, differentiation capabilities and transcriptomics. Our results indicated a greater presence of C-MSC in RV vs. LV total tissue. Moreover, more cells can be obtained from RV than from LV after isolation procedures. LV and RV C-MSC are characterized by the expression of the same surface markers. Functional studies revealed RV-LV C-MSC comparable groth curves but higher apoptosis rate within the LV cells. Moreover, higher propensity of the RV to to collagen deposition was obseved. Transcriptome analysis confirmed differences in the expression of genes related to apoptosis regulation and extracellular matrix organization. Alongside, we unveiled further pathways specifically associated to LV or RV C-MSC. Conclusions. These results contribute to understand the role of RV and LV C-MSC in physiological condition. Moreover, the obtained information can unravel their differential contribution to RV or LV- specific pathologic scenarios. RNA-Seq allowed identifying novel differentially expressed genes in RV vs. LV cells, which might uncover unappreciated mechanisms underlying ventricle-specific C-MSC regulation.
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Project description:RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor positive (ER+) breast cancer but their role in disease pathogenesis remains unclear. Herein we examined multiple in-frame and out-of-frame ESR1 fusions and found that two, both identified in advanced endocrine treatment resistant disease, encoded stable and functional in-frame fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, the N-terminal, DNA binding and dimerization motifs encoded by exons 2-6 were fused to C terminal sequences from the partner gene. Functional properties included estrogen-independent growth, constitutive expression of ER target genes, anti-estrogen resistance, induction of cellular motility in vitro and the development of lung metastasis in vivo. Chromatin immunoprecipitation and RNA sequencing experiments showed both fusions uniquely activated a metastasis-associated transcriptional program. ESR1-e6>YAP1 and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, palbociclib, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.
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Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling). Free-swelling MSC-seeded constructs were cultured for 21 days in chemically defined media. Chondrogenesis was induced with TGF-beta3. Undifferentiated controls were maintained in parallel. After 21 days of chondrogenic differentiation, a subset of constructs were subjected to 21 days of dynamic compressive loading. On days 21 and 42, construct mechanical properties and biochemical content were assessed. Microarray analysis was carried out on day 3, day 21 and day 42 constructs. 6 arrays.
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Project description:Ewings Sarcoma (ES) belongs to the group of bone cancers defined by the existence of a certain EWS-ETS fusion gene. In this study we use the model cell line CADO-ES1 (EWSR1-ERG fusion gene) to characterize the tumor biology of a versatile ES side-population (SP). We aim to compare SP- and non-SP-cells to identify specific characteristics of the SP which points towards a tumor driving functionality of the SP. Due to some stem cell like properties of the SP fraction a comparison to MSCs and normal fibroblasts as a control are also performed.
2017-10-31 | E-MTAB-6067 | biostudies-arrayexpress