Transcriptomic regulation of human mesenchymal stem cells in delivering anti-tumorigenic effects on leukaemic cell lines
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ABSTRACT:
PROVIDER: PRJNA479854 | ENA |
REPOSITORIES: ENA
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Project description:The present study was designed to investigate the effect of human umbilical cord-derived MSCs (UC-MSCs) on the proliferation of leukaemic cells and gauged the transcriptomic modulation and the signalling pathways that potentially inflicted by UC-MSCs.
2020-09-15 | GSE116677 | GEO
Project description:Tumorigenic iPSC-NS/PCs with mesenchymal properties
| PRJNA699371 | ENA
Project description:Treatment of leukemia has become much difficult because of resistance to the existing anticancer therapies. This has thus expedited the search for alternativ therapies, and one of these is the exploitation of mesenchymal stem cells (MSCs) towards control of tumor cells. The present study investigated the effect of human umbilical cord-derived MSCs (UC-MSCs) on the proliferation of leukemic cells and gauged the transcriptomic modulation and the signaling pathways potentially affected by UC-MSCs. The inhibition of growth of leukemic tumor cell lines was assessed by proliferation assays, apoptosis and cell cycle analysis. BV173 and HL-60 cells were further analyzed using microarray gene expression profiling. The microarray results were validated by RT-qPCR and western blot assay for the corresponding expression of genes and proteins. The UC-MSCs attenuated leukemic cell viability and proliferation in a dose-dependent manner without inducing apoptosis. Cell cycle analysis revealed that the growth of tumor cells was arrested at the G0/G1 phase. The microarray results identified that HL-60 and BV173 share 35 differentially expressed genes (DEGs) (same expression direction) in the presence of UC-MSCs. In silico analysis of these selected DEGs indicated a significant influence in the cell cycle and cell cycle-related biological processes and signaling pathways. Among these, the expression of DBF4, MDM2, CCNE2, CDK6, CDKN1A, and CDKN2A was implicated in six different signaling pathways that play a pivotal role in the anti-tumorigenic activity exerted by UC-MSCs. The UC-MSCs perturbate the cell cycle process of leukemic cells via dysregulation of tumor suppressor and oncogene expression.
| S-EPMC7444238 | biostudies-literature
Project description:T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy commonly driven by NOTCH1 activating mutations. A concomitant feature associated with NOTCH1 mutations is heightened oxidative metabolism enabling the exponential proliferation of T-ALL blasts. As such, targeting mitochondrial metabolism in T-ALL is an attractive therapeutic avenue. Canagliflozin (cana) is an FDA-approved sodium glucose co-transporter 2 inhibitor with known off-target effects on complex I and glutamate dehydrogenase. To date, the effects of cana on T-ALL are not known. Here, we show that cana possesses potent anti-leukaemic effects underpinned by proliferative defects, cell cycle disruption and apoptosis. These anti-leukaemic effects, driven by cana, are attributed to a perturbed tricarboxylic acid (TCA) cycle and mitochondrial metabolism and elevated mitochondrial ROS. Proteomic analysis revealed that cana treatment resulted in a compensatory increase in the expression of ATF4 targets, including upregulation of serine biosynthesis pathway and one-carbon metabolism enzymes. As such, restriction of serine and glycine synergized with cana treatment, further enhancing anti-leukaemic effects. Collectively, our study reveals cana creates a metabolic vulnerability that can be further exploited via dietary manipulation to treat T-ALL
2025-10-27 | PXD069587 | Pride
Project description:Generation of stable epithelial-mesenchymal hybrid cancer cells with tumorigenic potential
| PRJNA925545 | ENA
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells. A total of six canine primary osteosarcoma cell lines were used in this study. Three cell lines were capable of forming tumors when transplanted into mice (tumorigenic) and three cell lines were not capable of forming tumors upon transplant into mice (non-tumorigenic). The gene expression data is from the primary cell lines, not the transplanted cells. There were no reference cell lines or controls used in this study.
2014-05-22 | E-GEOD-57884 | biostudies-arrayexpress
Project description:In this manuscript, we used a non-genetically manipulated EMT/MET cell line model to demonstrate that epithelial mesenchymal plasticity occurring in normal cells generates co-existing phenotypically and functionally divergent cell subpopulations with increased tumorigenic potential in vivo.
2021-07-30 | GSE181008 | GEO
Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells.
2014-05-22 | GSE57884 | GEO
Project description:We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
2017-07-12 | GSE78234 | GEO
Project description:Comparison of chromosome region copy number changes accompanying progression of immortalized MLL-ENL expressing cells into leukaemic cells
2008-11-20 | E-MEXP-1911 | biostudies-arrayexpress