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Updated: Aug 14, 2025
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice
Flavia A Graca1, Anna Stephan1, Yong-Dong Wang2
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Solid Tumor Program, Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues is largely unknown. Here, we find that the heart and skeletal muscle undergo wasting at early stages and are the tissues transcriptionally most impacted by cachexia. We also identify general and organ-specific transcriptional changes that indicate functional derangement by cachexia even in tissues that do not undergo wasting, such as the brain. Secreted factors constitute a top category of cancer-regulated genes in host tissues, and these changes include upregulation of the angiotensin-converting enzyme (ACE). ACE inhibition with the drug lisinopril improves muscle force and partially impedes cachexia-induced transcriptional changes, although wasting is not prevented, suggesting that cancer-induced host-secreted factors can regulate tissue function during cachexia. Altogether, by defining prevalent and temporal and tissue-specific responses to cachexia, this resource highlights biomarkers and possible targets for general and tissue-tailored anti-cachexia therapies.
Insights
Cachexia significantly impacts heart and skeletal muscle early on, altering tissue function. Targeting secreted factors like angiotensin-converting enzyme (ACE) may offer therapeutic benefits for this cancer-associated wasting syndrome.
Area of Science:
- Oncology
- Physiology
- Molecular Biology
Background:
- Cachexia is a critical factor in cancer mortality, characterized by systemic wasting.
- The progressive and differential impact of cachexia on various tissues remains poorly understood.
Purpose of the Study:
- To investigate the tissue-specific and temporal effects of cachexia.
- To identify molecular mechanisms and potential therapeutic targets for cachexia.
Main Methods:
- Transcriptional profiling of multiple tissues in a cachexia model.
- Analysis of secreted factors and their role in cachexia.
- Pharmacological intervention using ACE inhibitors.
Main Results:
- Heart and skeletal muscle are early targets of wasting and transcriptional changes in cachexia.
- Cachexia induces functional derangement in non-wasting tissues like the brain.
- Upregulation of angiotensin-converting enzyme (ACE) was observed; ACE inhibition partially improved muscle function and transcriptional profiles.
Conclusions:
- Cachexia causes widespread transcriptional dysregulation and functional impairment across tissues.
- Secreted factors, including ACE, play a role in mediating cachexia's effects.
- Targeting ACE and other secreted factors may offer novel therapeutic strategies for cachexia.
