Related Experiment Video
Updated: Jun 6, 2026
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine
Caterina Constantinou1, Cibely Cristine Fontes de Oliveira, Dionyssios Mintzopoulos
1NMR Surgical Laboratory, Massachusetts General and Shriners Hospitals, Harvard Medical School, Boston, MA 02114, USA.
Abstract:
Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce metabolic changes in the host that lead to massive loss in skeletal muscle mass. Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant expression in skeletal muscle. Mice implanted with Lewis lung carcinomas were examined by in vivo 31P nuclear magnetic resonance (NMR). We examined ATP synthesis rate and the expression of genes that play key-regulatory roles in skeletal muscle metabolism. Our in vivo NMR results showed reduced ATP synthesis rate in tumor-bearing (TB) mice relative to control (C) mice, and were cross-validated with whole genome transcriptome data showing atypical expression levels of skeletal muscle regulatory genes such as peroxisomal proliferator activator receptor γ coactivator 1 ß (PGC-1ß), a major regulator of mitochondrial biogenesis and, mitochondrial uncoupling protein 3 (UCP3). Aberrant pattern of gene expression was also associated with genes involved in inflammation and immune response, protein and lipid catabolism, mitochondrial biogenesis and uncoupling, and inadequate oxidative stress defenses, and these effects led to cachexia. Our findings suggest that reduced ATP synthesis is linked to mitochondrial dysfunction, ultimately leading to skeletal muscle wasting and thus advance our understanding of skeletal muscle dysfunction suffered by cancer patients. This study represents a new line of research that can support the development of novel therapeutics in the molecular medicine of skeletal muscle wasting. Such therapeutics would have wide-spread applications not only for cancer patients, but also for many individuals suffering from other chronic or endstage diseases that exhibit muscle wasting, a condition for which only marginally effective treatments are currently available.
Insights
Cancer cachexia causes significant skeletal muscle wasting due to reduced ATP synthesis and aberrant gene expression. This study reveals mitochondrial dysfunction as a key driver of muscle loss in cancer patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer cachexia is a debilitating syndrome characterized by severe skeletal muscle mass loss.
- Tumors induce metabolic alterations in the host, contributing to muscle wasting.
- Understanding the molecular mechanisms underlying cachexia is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of tumor inoculation on ATP synthesis and gene expression in skeletal muscle.
- To test the hypothesis that cancer cachexia involves reduced ATP production and aberrant gene regulation.
- To explore the role of mitochondrial dysfunction in cancer-induced muscle wasting.
Main Methods:
- Utilized a preclinical mouse model implanted with Lewis lung carcinomas.
- Employed in vivo 31P nuclear magnetic resonance (NMR) to assess ATP synthesis rates.
- Conducted whole genome transcriptome analysis to examine gene expression patterns in skeletal muscle.
Main Results:
- Demonstrated a reduced ATP synthesis rate in tumor-bearing mice compared to controls.
- Identified aberrant expression of key skeletal muscle regulatory genes, including PGC-1ß and UCP3.
- Observed altered gene expression related to inflammation, catabolism, mitochondrial function, and oxidative stress.
Conclusions:
- Reduced ATP synthesis is linked to mitochondrial dysfunction, driving skeletal muscle wasting in cancer cachexia.
- Aberrant gene expression patterns contribute to the metabolic derangements observed in cachexia.
- Findings provide insights into the molecular basis of muscle wasting and support novel therapeutic development for cancer patients and other chronic diseases.
