Related Experiment Video
Updated: Jun 24, 2025
08:55
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
16.2K
Area postrema neurons mediate interleukin-6 function in cancer cachexia
Qingtao Sun1, Daniëlle van de Lisdonk1,2, Miriam Ferrer1
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
Nature Communications
|June 1, 2024
Summary
Interleukin-6 (IL-6) in the brainstem area postrema (AP) drives cancer cachexia. Targeting IL-6 signaling in AP neurons alleviates symptoms and extends lifespan in mice.
Area of Science:
- Neuroscience
- Oncology
- Physiology
Background:
- Interleukin-6 (IL-6) is implicated in cancer cachexia, a wasting syndrome.
- The precise mechanism by which peripheral IL-6 affects the brain to cause cachexia is unclear.
Purpose of the Study:
- To investigate the role of the area postrema (AP) in mediating IL-6 effects in cancer cachexia.
- To identify therapeutic targets for cancer cachexia.
Main Methods:
- Used male mice with peripheral tumors.
- Administered anti-IL-6 antibodies and employed CRISPR/dCas9 interference and Gfral neuron silencing in the AP.
- Measured IL-6 levels, synaptic transmission, network activity, cachectic phenotypes, and lifespan.
Main Results:
- Circulating IL-6 rapidly enters the AP and activates its neurons.
- Tumor-induced IL-6 increases IL-6 in the AP, potentiating synaptic transmission and causing network hyperactivity.
- Neutralizing IL-6 in the brain, suppressing IL-6 receptor (Il6ra) in AP neurons, or silencing Gfral-expressing AP neurons attenuated cachexia, reduced AP network hyperactivity, and prolonged lifespan.
Conclusions:
- Neurons in the AP are critical mediators of IL-6-induced cancer cachexia.
- Targeting IL-6 signaling within the AP offers a potential therapeutic strategy for cancer cachexia.
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