ArticleJournal of cachexia, sarcopenia and muscle2023
A novel orthotopic mouse model replicates human lung cancer cachexia.
Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- The Secretome of a Cachexia-Inducing Lung Tumor Impairs Mitochondrial Function and Skeletal Muscle Differentiation.Cancers · 2026Article
- The Effect of Dietary Fiber Compositions on the Therapeutic Outcome of Combined Radio- and Immunotherapy in a Preclinical Cancer Model.Molecular nutrition & food research · 2026Article
- Establishment and characterization of an orthotopic implanted lung cancer model to mimic human tumor structure, microenvironment, and metastatic spread.Translational lung cancer research · 2025Article
- Cathepsin L as a dual-target to mitigate muscle wasting while enhancing anti-tumor efficacy of anti-PD-L1.Nature communications · 2025Article
- Early adipose tissue wasting in a preclinical model of human lung cancer cachexia.Cell reports · 2025Article
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- Ensemble methods and partially-supervised learning for accurate and robust automatic murine organ segmentation.Scientific reports · 2025Article
- Cancer cachexia: multilevel metabolic dysfunction.Nature metabolism · 2024Review
- Targeted nutritional intervention attenuates experimental lung cancer cachexia.Journal of cachexia, sarcopenia and muscle · 2024Article
- Molecular Mechanisms of Cachexia: A Review.Cells · 2024Review
- Harnessing the Systemic Biology of Functional Decline and Cachexia to Inform more Holistic Therapies for Incurable Cancers.Cancers · 2024Review
- The impact of sarcopenia on the efficacy of PD-1 inhibitors in non-small cell lung cancer and potential strategies to overcome resistance.Frontiers in pharmacology · 2024Review
- Oncometabolite D-2-hydroxyglutarate-dependent metabolic reprogramming induces skeletal muscle atrophy during cancer cachexia.Communications biology · 2023Article
- A novel orthotopic mouse model replicates human lung cancer cachexia.Journal of cachexia, sarcopenia and muscle · 2023Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCancer cachexia, highly prevalent in lung cancer, is a debilitating syndrome characterized by involuntary loss of skeletal muscle mass and is associated with poor clinical outcome, decreased survival and negative impact on tumour therapy. Various lung tumour-bearing animal models have been used to explore underlying mechanisms of cancer cachexia. However, these models do not simulate anatomical and immunological features key to lung cancer and associated muscle wasting. Overcoming these shortcomings is essential to translate experimental findings into the clinic. We therefore evaluated whether a syngeneic, orthotopic lung cancer mouse model replicates systemic and muscle-specific alterations associated with human lung cancer cachexia.
methodsImmune competent, 11 weeks old male 129S2/Sv mice, were randomly allocated to either (1) sham control group or (2) tumour-bearing group. Syngeneic lung epithelium-derived adenocarcinoma cells (K-ras
resultsTwo-third of the tumour-bearing mice developed cachexia based on predefined criteria. Final body weight (-13.7 ± 5.7%; P < 0.01), muscle mass (-13.8 ± 8.1%; P < 0.01) and muscle strength (-25.5 ± 10.5%; P < 0.001) were reduced in cachectic mice compared with sham controls and median survival time post-surgery was 33.5 days until humane endpoint. Markers for proteolysis, both ubiquitin proteasome system (Fbxo32 and Trim63) and autophagy-lysosomal pathway (Gabarapl1 and Bnip3), were significantly upregulated, whereas markers for protein synthesis (relative phosphorylation of Akt, S6 and 4E-BP1) were significantly decreased in the skeletal muscle of cachectic mice compared with control. The cachectic mice exhibited increased pentraxin-2 (P < 0.001) and CXCL1/KC (P < 0.01) expression levels in blood plasma and increased mRNA expression of IκBα (P < 0.05) in skeletal muscle, indicative for the presence of systemic inflammation. Strikingly, RNA sequencing, pathway enrichment and miRNA expression analyses of mouse skeletal muscle strongly mirrored alterations observed in muscle biopsies of patients with lung cancer cachexia.
conclusionsWe developed an orthotopic model of lung cancer cachexia in immune competent mice. Because this model simulates key aspects specific to cachexia in lung cancer patients, it is highly suitable to further investigate the underlying mechanisms of lung cancer cachexia and to test the efficacy of novel intervention strategies.
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