CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: ‘in vitro’ and ‘in silico’ approaches inside a spiderweb interaction network
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223853 | GEO | 2023/07/19
REPOSITORIES: GEO
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Project description:CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: ‘in vitro’ and ‘in silico’ approaches inside a spiderweb interaction network
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Project description:To investigate whether conditioned medium (CM) from cancer cell culture impacts dynamic changes of the transcriptome in myotubes differentiated from hMuSC, we ran RNA sequencing from differentiated hMuSC that were treated by multiple breast cancer cell lines-conditioned medium. Among 14208 readable mRNAs, MCF-7 CM treatment induced significant changes in 2680 genes, MB-468 CM caused significant changes in 2674 genes, and SKBR-3 CM resulted in significant changes in 1823 genes in myotubes from differentiated hMuSC, compared to control group, respectively. Among them, 961 genes had significant upregulation or downregulation presented in differentiated myotubes over all 3 breast cancer cell lines CMs
2023-05-03 | GSE206662 | GEO
Project description:Bone metastases is a common severe complication for breast cancer. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced breast cancer cell extravasation across endothelial monolayers. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. Therefore, we used RNA sequencing to show that CM from endothelial cells conditioned in CM from flow-stimulated osteocytes significantly altered gene expression in bone-metastatic breast cancer cells. This This provides insights into the capability of bone-loading activity in preventing bone metastases.
2018-11-13 | E-MTAB-7176 | biostudies-arrayexpress
Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-α, MCP-1, RANTES, and IL-1α is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC.
2012-12-01 | GSE35901 | GEO
Project description:The disturbance of adipose tissue in obesity highly correlates with cancer progression. To investigate the impacts of obesity on triple-negative breast cancer (TNBC), we performed an in vitro system culturing TNBC cells with human white adipocytes-conditioned medium (hAd-CM). The gene expression profiling between each condition was then assessed by RNA-seq.
2023-01-25 | GSE209894 | GEO
Project description:Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate this, eight-week-old male C57BL/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200 µm slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression via RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomic analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like Growth Factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis.
2022-02-17 | PXD027332 | Pride
Project description:To investigate TGFβ1 (a key member of the TGFβ superfamily) signaling in non-cancerous and cancerous cells derived from breast epithelium and what further response it might generate, we treated the cells with TGFβ1 or with conditioned media. We selected MCF10A non-tumorigenic breast epithelial cells (isolated from the mammary gland with fibrocystic disease) and MCF7 breast adenocarcinoma cells (estrogen receptor-positive, ER+). We followed a regimen of treating the cells for six consecutive days, with daily administration of TGFβ1 for two hours. The TGFβ1-containing medium was changed to a fresh one, which was collected after another 22 hours (so-called conditioned medium, CM) and administered to other cells. This enabled us to assess the ability of extracellularly secreted molecules to further induce a cellular response (bystander effect). RNA-seq analyses were performed on cells either directly treated with TGFβ1 in the above scheme or treated with a conditioned media for 1, 2, 3, 4, 5, or 6 days. The experiment was performed in three biological replicates, and each sample was sequenced separately. RNA-seg analysis in both cell lines allowed us to find the differences and similarities in response to TGFβ1 and CM. All 84 libraries were sequenced on Illumina NovaSeq6000 platform, in 2x150 mode, with a coverage of 60M reads/sample.
2024-12-01 | E-MTAB-13865 | biostudies-arrayexpress
Project description:To elucidate molecular mechanisms underlying brain metastasis-promoting function of Cdk5, two analyses were performed. In the first analysis, we screened for Cdk5 substrates in brain-seeking breast cancer cell lines 4T1.Br3 and T11.Br1, transfected with shRNA targeting Cdk5 mRNA (100% knockdown) or control. T11.Br1 and 4T1.Br3 cells (shCDK5 or shCtl) were cultured for 6 days in the presence of labelled arginine and lysine from the SILAC Protein Quantitation Kit. For the second analysis, we performed a quantitative label-free mass-spectrometry analysis of astrocytes’ conditioned media pre-educated by 4T1.Br3 cell-derived CM for 72 h. For the second analysis, we performed a quantitative label-free mass-spectrometry analysis of astrocytes’ conditioned media pre-educated by 4T1.Br3 cell-derived CM for 72 h.
2024-06-28 | PXD053434 | Pride
Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-M-NM-1, MCP-1, RANTES, and IL-1M-NM-1 is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC. The microRNA expression of migratory subpopulations were compared to parental populations of MSCs.
2012-12-01 | E-GEOD-35901 | biostudies-arrayexpress
Project description:Exosomes are nanoparticles secreted by all cell types and are a large component of the broader class of nanoparticles termed extracellular vesicles (EVs). Once secreted, exosomes gain access to the interstitial space and ultimately the circulation, where they exert local paracrine or distal systemic effects. Because of this, exosomes are important components of an intercellular and intraorgan communication system capable of carrying biologic signals from one cell type or tissue to another. The exosomal cargo consists of proteins, lipids, miRNAs, and other RNA species, and many of the biologic effects of exosomes have been attributed to miRNAs. Exosomal miRNAs have also been used as disease biomarkers. The field of exosome biology and metabolism is rapidly expanding, with new discoveries and reports appearing on a regular basis, and it is possible that potential therapeutic approaches for the use of exosomes or miRNAs in metabolic diseases will be initiated in the near future.
| S-EPMC8428804 | biostudies-literature