Next Generation Sequencing of mRNA of cachectic mice muscles in C26 model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE175570 | GEO | 2021/05/27
REPOSITORIES: GEO
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Project description:Cancer mediated activation of the ActRIIB-ALK4/5 heterodimer by myostatin is strongly associated with muscle wasting. Progressive skeletal muscle wasting, with or without loss of adipose tissue, is observed in up to 50 per cent of all cancer patients. This multifactorial syndrome is known as cachexia, and cannot be fully reversed by conventional nutritional support. Cachexia leads to progressive functional impairment. We investigated in vitro and in vivo the efficacy of ALK4/5 receptor blockers like SB431542 in preventing muscle wasting and in this context determined muscle-related miRNA expression profiles in non-tumor bearing control mice, in SB431542 treated C26 tumor-bearing mice and in cachectic C26 tumor-bearing mice.
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Project description:The IL-6 was reported as a key cachectic factor in mice inoculated with colon carcinoma 26 (C26) cells, a widely used cancer cachexia model. However, we identified We found that the growth of IL-6 KO tumors was dramatically delayed. More strikingly, while IL-6 KO tumors eventually reached the similar size as wild-type tumors, cachexia still took place, despite no elevation in circulating IL-6. We further showed that IL-6 promotes tumor growth by facilitating immune evatioon but is dispensable for cachexia.
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Project description:We surveyed the transcriptomes of the whole heart and whole gastrocnemius muscle taken from two different types of Balb/c-DBAj hybrid mice (10-11 weeks old). The colon cancer bearing mice are called C26. The NTB are the non-tumor bearing mice. This dataset includes Affymetrix expression data collected from the biological triplicates of heart and gastrocnemius from both C26 and NTB mice.
2014-11-10 | GSE63032 | GEO
Project description:Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-ĸB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. A LIF blocking antibody abolished C26 CM-induced STAT reporter activation STAT3 phosphorylation and myotube atrophy, but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked the C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together these data support an important role of LIF- JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. from three replicate wells of cells at each treatment, pools of total RNA were used to create cDNA which were evaluated on Affymetrix mouse gene 1.0 ST v.1 arrays.
2015-06-25 | E-GEOD-68827 | biostudies-arrayexpress
Project description:Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-ĸB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. A LIF blocking antibody abolished C26 CM-induced STAT reporter activation STAT3 phosphorylation and myotube atrophy, but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked the C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together these data support an important role of LIF- JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.
2015-06-25 | GSE68827 | GEO
Project description:We found out that bile acid pathways were deeply altered in cachectic mice bearing ectopic tumor, leading to an increase in portal and liver conjugated bile acid levels. Counteracting this increased level in conjugated bile acids using cholestyramine, a bile acid sequestrant, reduced hepatic inflammation in cachectic mice with no impact on steatosis and minor effects on thermogenesis. Hepatic whole transcriptome analysis identified 16 pathways altered in cachectic mice which were counteracted by cholestyramine, pointing out the large contribution of bile acids to hepatic disturbances occurring in cancer cachexia.
2021-02-24 | GSE154219 | GEO
Project description:Analysis of gene expression in CD2F1 mice with cancer cachexia due to implantation of C26 colon carcinoma cells. Total RNA obtained from quadriceps muscle of female CD2F1 mice with early weight loss (10%) or severe weight loss (15%) due to intrascapular subcutaneous implantation of one million C26 colon adenocarcinoma cells.
2011-08-29 | E-GEOD-24112 | biostudies-arrayexpress
Project description:Cachexia is a devastating muscle wasting syndrome that occurs in patients suffering from chronic diseases, most commonly observed in 80% of advanced cancer patients. One of the primary causes of cachexia-associated morbidity and mortality is involuntary muscle wasting. And while many cachexia patients show hypermetabolism, its causative role in muscles had remained unclear. To understand the molecular basis of this muscle wasting, accurate models of cachexia are necessary. Using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors which rapidly led to higher levels of fatty acid metabolism and the activation of a p38 stress response signature, before the cachectic muscle wasting is manifested. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, leading to oxidative stress, p38 activation, and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also significantly improved muscle mass and total weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer cachexia.
2016-05-01 | GSE80081 | GEO
Project description:Background Loss of skeletal muscle mass in advanced cancer is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are still lacking. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in muscle proteome and secretome associated with cancer-induced cachexia to better understand cellular mechanisms involved in this wasting process and to identify secreted proteins which might reflect the ongoing muscle atrophy process. Methods We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Selected reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Their muscle source was demonstrated by assessing their gene expression in skeletal muscle and in cultured myotubes. Finally, we also investigated their regulation in muscle cells. Alterations in several molecular pathways potentially involved in muscle atrophy were highlighted using Gene ontology enrichment analyses. Results Our results revealed a dramatic increased production (2-to 25-fold) by the muscle of several acute phase reactants (APR: Haptoglobin, Serpina3n, Complement C3, Serum amyloid A1) which are also released in the circulation during C26 cancer cachexia. Their production was confirmed in other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Glucocorticoids and pro-inflammatory cytokines contribute directly to their increased expression in muscle cells in vitro, while the role of IL-6 in the muscular induction of these APR was demonstrated in vivo. Conclusions Cancer is associated with marked changes in muscle secretome during muscle wasting. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.
2020-10-28 | PXD016474 | Pride
Project description:Next Generation Sequencing of mRNA of cachectic mice muscles in C26 model
| PRJNA732917 | ENA