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.
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Project description:Nitro-fatty acids (NFAs) are endogenously formed lipid mediators that cause a broad spectrum of anti-inflammatory effects by covalent modification of key proteins within inflammatory signaling pathways. Their potential as therapeutics has been demonstrated in numerous animal models of disease. Herein, we evaluated the anti-tumorigenic effects of NFAs in the colon carcinoma cell line Caco-2 and other solid and leukemic tumor cell lines. NFAs inhibited the ubiquitin–proteasome system (UPS), leading to polyubiquitination and inhibition of the proteasome activities. Suppression of the UPS induced the pro-apoptotic transcription factor CHOP by activation of the unfolded protein response (UPR), resulting in tumor cell death. NFA-mediated effects on UPS and UPR were rather strong, highly specific, largely irreversible, and represent a mechanistically new mode of action for pharmacological suppression of the UPS. Taking into account their favorable safety profile in clinical phase I trials in combination with their well-recognized anti-tumorigenic efficacy covering solid tumors, we conclude that NFAs are innovative proteasome inhibitor drug candidates that may have a large potential to overcome the limitations of the classical proteasome inhibitors.
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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:Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1 and LMP7 is expressed in most immune cells. In this study we describe two opposing roles for immunoproteasomes in regulating the tumor microenvironment. During chronic inflammation, immunoproteasomes modulated the expression of pro-tumorigenic cytokines and chemokines and enhanced infiltration of innate immune cells that led to the onset of colitis-associated carcinogenesies (CAC). In ulcerative colitis (UC) patients with high risk for CAC, immunoproteasome-induced pro-tumorigenic mediators were highly upregulated. Interestingly, the role for the same enzymatic complex in melanoma tumors is relatively unknown. We found that the high expression of immunoproteasomes in human melanoma was associated with better prognosis. Our data revealed that the immunoproteasome has a strong anti-tumorigenic function in cancer types with non-inflammatory microenvironment such as melanoma. CD8+ cytotoxic T lymphocytes (CTLs) from immunoproteasome-deficient mice were reduced during T cell homeostasis and were not able to combat melanoma efficiently. Our results indicate that the immunoproteasome exhibits either pro- or anti-tumoral properties in a context-dependent manner.
2021-08-18 | GSE150979 | GEO
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:SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine
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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