Molecular characterization of cachexia in a novel head and neck cancer mouse model
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PROVIDER: PRJNA1217823 | ENA |
REPOSITORIES: ENA
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Project description:Despite accounting for only ~4% of all cancers in the US, experimental and clinical observations suggest that ~40% of patients with head and neck cancer (HNC) present with ‘cachexia’, a severe comorbidity that associates with skeletal muscle defects and is responsible for decreased muscle function, worsened response to treatment, and poorer outcomes. Despite its clinical relevance, the mechanism(s) responsible for the onset of cachexia in HNC patients are not completely understood, thus leading to limited progress in diagnosis and representing a barrier to the development of treatments. Moreover, impeding the identification of viable therapies to combat HNC cachexia is also the limited availability of small animal models. Here, we characterized molecular and functional features of cachexia in a novel, preclinical model for the study of HNC, namely the mouse bearing the B0092 oral squamous cell carcinoma, transplantable in recipient C57BL/6 mice To investigate the systemic effects of HNC tumors, 10-week-old C57BL/6 male mice were implanted with B0092 cells (5x105 cells, s.c.) and monitored for up to 36 days. Growth of B0092 tumors was accompanied by skeletal muscle atrophy, loss of Extensor Digitorum Longus (EDL) muscle strength, reduced bone mineral density (BMD), measured by DEXA, and decreased trabecular bone, assessed using microCT. To identify the gene signature associated with muscle wasting caused by B0092 tumors, we performed Next Gen RNA-Sequencing of quadriceps muscle. The pathway analysis conducted using the Ingenuity Pathway Analysis (IPA) and integrated Differential Expression and Pathway (iDEP) bioinformatic tools, revealed dysfunction of mitochondria, as well as upregulation of proteasome- and translation-related pathways. In conclusion, our data suggests that B0092-bearing mice can be a useful tool to uncover novel molecular pathways and potential therapeutic targets for the treatment of HNC cachexia.
2025-08-20 | GSE288471 | GEO
Project description:To provide full characterization of genome changes in six commonly used head and neck cancer cell lines. These data will serve as an excellent resource when designing future experiments that attempt to model HNSCC behaviour. Six commonly used ATCC head and neck cancer cell lines are analyzed.
2010-06-25 | E-GEOD-16872 | biostudies-arrayexpress
Project description:To provide full characterization of genome changes in six commonly used head and neck cancer cell lines. These data will serve as an excellent resource when designing future experiments that attempt to model HNSCC behaviour.
2010-06-26 | GSE16872 | GEO
Project description:BackgroundCancer cachexia is a metabolic disorder characterized by the progressive loss of fat and lean mass that results in significant wasting, ultimately leading to reduced quality of life and increased mortality. Effective therapies for cachexia are lacking, potentially owing to the mismatch in clinically relevant models of cachexia. Specifically, cachexia observed in a clinical setting is commonly associated with advanced or late-stage cancers that are metastatic, yet pre-clinical metastatic models of cachexia are limited. Furthermore, the prevalence of cachexia in head and neck cancer patients is high, yet few pre-clinical models of head and neck cancer cachexia exist. In addition to these shortcomings, cachexia is also heterogeneous among any given cancer, whereas patients with similar disease burden may experience significantly different degrees of cachexia symptoms. In order to address these issues, we characterize a metastatic model of human papilloma virus (HPV) positive head and neck squamous cell carcinoma that recapitulates the cardinal clinical and molecular features of cancer cachexia.MethodsMale and female C57BL/6 mice were implanted subcutaneously with oropharyngeal squamous cell carcinoma cells stably transformed with HPV16 E6 and E7 together with hRas and luciferase (mEERL) that metastasizes to the lungs (MLM). We then robustly characterize the physiologic, behavioural, and molecular signatures during tumour development in two MLM subclones.ResultsMice injected with MLM tumour cells rapidly developed primary tumours and eventual metastatic lesions to the lungs. MLM3, but not MLM5, engrafted mice progressively lost fat and lean mass during tumour development despite the absence of anorexia (P < 0.05). Behaviourally, MLM3-implanted mice displayed decreased locomotor behaviours and impaired nest building (P < 0.05). Muscle catabolism programmes associated with cachexia, including E3 ubiquitin ligase and autophagy up-regulation, along with progressive adipose wasting and accompanying browning gene signatures, were observed. Tumour progression also corresponded with hypothalamic and peripheral organ inflammation, as well as an elevation in neutrophil-to-lymphocyte ratio (P < 0.05). Finally, we characterize the fat and lean mass sparing effects of voluntary wheel running on MLM3 cachexia (P < 0.05).ConclusionsThis syngeneic MLM3 allograft model of metastatic cancer cachexia is reliable, consistent, and readily recapitulates key clinical and molecular features and heterogeneity of cancer cachexia. Because few metastatic models of cachexia exist-even though cachexia often accompanies metastatic progression-we believe this model more accurately captures cancer cachexia observed in a clinical setting and thus is well suited for future mechanistic studies and pre-clinical therapy development for this crippling metabolic disorder.
| S-EPMC8517353 | biostudies-literature
Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers
2022-03-01 | PXD001438 | Pride
Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue comparative analysis of gene expression profiles of head and neck squamous cell carcinoma and Head and Neck normal tissue
2008-09-30 | E-GEOD-11986 | biostudies-arrayexpress
Project description:Analysis of the genes involved in the metastasis of head and neck squamous cell carcinoma (HNSCC). We hypothesized that there would be overexpression of certain genes in the highly metastatic USC-HN1-GFP-G1 and USC-HN1-GFP-G2 cell lines compared to the parental USC-HN1-GFP cell line.
2012-10-29 | GSE41893 | GEO
Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
2011-10-27 | E-GEOD-25083 | biostudies-arrayexpress
Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue
2008-09-30 | GSE11986 | GEO
Project description:Quantitative redox proteomics analysis was performed using the SCC-61/rSCC-61 matched model system of radiation resistance in human head and neck squamous cell carcinoma.
2023-03-10 | PXD029053 | Pride