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Updated: Apr 28, 2026
The In ovo CAM-assay as a Xenograft Model for Sarcoma
Published on: July 17, 2013
Daily rhythms are retained both in spontaneously developed sarcomas and in xenografts grown in immunocompromised SCID
Maria Comas1, Karen K Kuropatwinski, Michelle Wrobel
1Department of Molecular and Cellular Biology, Roswell Park Cancer Institute , Buffalo, NY , USA .
Abstract:
The circadian clock generates and regulates many daily physiological, metabolic and behavioral rhythms as well as acute responses to various types of stresses including those induced by anticancer treatment. It has been proposed that modulatory function of the clock may be used for improving the therapeutic efficacy of established anti-cancer treatments. In order to rationally exploit this mechanism, more information is needed to fully characterize the functional status of the molecular clock in tumors of different cellular origin; however, the data describing tumor clocks are still inconsistent. Here we tested the status of clock in two models of tumors derived from connective tissue: sarcomas spontaneously developed in p53-deficient mice and human fibrosarcoma cells grown as xenografts in immunocompromised severe combined immunodeficient (SCID) mice. We show that both types of tumors retain a functional clock, which is synchronized in phase with normal tissues. We also show that spontaneously developed tumors are not only oscillating in the context of an organism where they receive hormonal and metabolic signals but continue oscillating ex vivo in tissue explants demonstrating that tumors have functional clocks capable of timing all their functions. We also provide evidence that similar to liver, tumors can be synchronized by food availability independent of the central pacemaker in the suprachiasmatic nuclei (SCN). These data provide the basis for the design of anticancer therapies that take into account the circadian metabolic and physiological patterns of both the tumor and normal tissues.
Insights
Cancer cells possess functional circadian clocks, synchronized with normal tissues. This discovery opens avenues for chronotherapy, optimizing anti-cancer treatments by aligning with tumor and body rhythms.
Area of Science:
- Chronobiology
- Cancer Research
- Molecular Oncology
Background:
- The circadian clock regulates physiological and behavioral rhythms, influencing stress responses, including those from anticancer treatments.
- Modulating the circadian clock may enhance anticancer therapy efficacy, but tumor clock status data are inconsistent.
- Understanding tumor molecular clocks is crucial for developing chronotherapeutic strategies.
Purpose of the Study:
- To investigate the functional status of the molecular clock in two connective tissue tumor models.
- To determine if tumor clocks are synchronized with normal tissues and can function independently.
- To explore potential synchronization of tumor clocks by factors like food availability.
Main Methods:
- Analysis of spontaneously developed sarcomas in p53-deficient mice.
- Assessment of human fibrosarcoma xenografts in severe combined immunodeficient (SCID) mice.
- Ex vivo tissue explant experiments to evaluate autonomous clock function.
Main Results:
- Both sarcoma and fibrosarcoma models exhibit functional circadian clocks.
- Tumor clocks were synchronized in phase with normal host tissues.
- Tumors demonstrated autonomous clock oscillations ex vivo and synchronization by food intake, independent of the suprachiasmatic nucleus (SCN).
Conclusions:
- Tumors possess functional, synchronized circadian clocks.
- Tumor clocks can be influenced by external cues like feeding, independent of the central pacemaker.
- These findings support the development of chronotherapy strategies for cancer treatment.
