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Host circadian clock as a control point in tumor progression.
Elisabeth Filipski1, Verdun M King, XiaoMei Li
1Institut National de la Santé et de la Recherche Médicale, Equipe Propre INSERM 0118 Cancer chronotherapeutics, Université Paris XI, Paul Brousse Hospital, Villejuif, France.
Journal of the National Cancer Institute
|May 2, 2002
Summary
Disrupting the circadian timing system by destroying the suprachiasmatic nuclei (SCN) in mice accelerated tumor growth and reduced survival. This highlights the circadian clock's role in controlling cancer progression.
Area of Science:
- Chronobiology
- Oncology
- Neuroscience
Background:
- The suprachiasmatic nuclei (SCN) regulate daily rhythms crucial for physiological processes.
- Altered circadian rhythms are linked to poorer survival in metastatic cancers.
- A mouse model was created to study circadian dysfunction's impact on tumor growth.
Purpose of the Study:
- To investigate the consequences of severe circadian dysfunction on tumor progression.
- To determine the role of the host circadian clock in endogenous tumor control.
Main Methods:
- Bilateral electrolytic lesions were used to destroy the SCN in mice.
- Rest-activity, body temperature, corticosterone, and lymphocyte counts were monitored.
- Mice were inoculated with osteosarcoma or pancreatic adenocarcinoma tumors.
Main Results:
- SCN lesions ablated the rest-activity cycle and altered daily rhythms of corticosterone and lymphocytes.
- Tumor growth was 2-3 times faster in mice with SCN lesions compared to controls.
- Survival was significantly shorter in mice with disrupted circadian rhythms.
Conclusions:
- Disruption of circadian rhythms accelerates the growth of malignant tumors.
- The host circadian clock plays a significant role in the endogenous control of tumor progression.