Circadian disruption induced by tumor development in a murine model of melanoma
Abstract: The circadian system induces oscillations in most physiological variables, with periods close to 24 hours. Dysfunctions in clock-controlled body functions, such as sleep disorders, as well as deregulation of clock gene expression or glucocorticoid levels have been observed in cancer patients. Moreover, these disorders have been associated with a poor prognosis or worse response to treatment. This work explored the circadian rhythms at behavioral and molecular levels in a murine melanoma model induced by subcutaneous inoculation of B16 tumoral cells. We observed that the presence of the tumors induced a decrease in the sturdiness of the locomotor activity rhythms and in the amount of nighttime activity, together with a delay in the acrophase and in the activity onset. Moreover, these differences were more marked when the tumor size was larger than in the initial stages of the tumorigenesis protocol. In addition, serum glucocorticoids, which exhibit strong clock-controlled rhythms, lost their circadian patterns. Similarly, the rhythmic expression of the clock genes Bmal1 and Cry1 in the hypothalamic Suprachiasmatic Nuclei (SCN) were also disrupted in mice carrying tumors. Altogether, these results suggest that tumor-secreted molecules (i.e., tumor macroenvironment) could modulate the function of the central circadian pacemaker (SCN). This could account for the worsening of the peripheral biological rhythms such as locomotor activity or serum glucocorticoids. Since disruption of the circadian rhythms might accelerate tumorigenesis, monitoring circadian patterns in cancer patients could offer a new tool to get a better prognosis for this disease.
| Main Authors: | , , , , |
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| Format: | Artículo biblioteca |
| Language: | eng |
| Published: |
Taylor & Francis
2021
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| Subjects: | RITMO CIRCADIANO, TUMORES, CANCER, GLUCOCORTICOIDES, |
| Online Access: | https://repositorio.uca.edu.ar/handle/123456789/12808 |
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| Summary: | Abstract: The circadian system induces oscillations in most physiological variables, with
periods close to 24 hours. Dysfunctions in clock-controlled body functions, such
as sleep disorders, as well as deregulation of clock gene expression or
glucocorticoid levels have been observed in cancer patients. Moreover, these
disorders have been associated with a poor prognosis or worse response to
treatment. This work explored the circadian rhythms at behavioral and molecular
levels in a murine melanoma model induced by subcutaneous inoculation of B16
tumoral cells. We observed that the presence of the tumors induced a decrease in
the sturdiness of the locomotor activity rhythms and in the amount of nighttime
activity, together with a delay in the acrophase and in the activity onset.
Moreover, these differences were more marked when the tumor size was larger
than in the initial stages of the tumorigenesis protocol. In addition, serum
glucocorticoids, which exhibit strong clock-controlled rhythms, lost their
circadian patterns. Similarly, the rhythmic expression of the clock genes Bmal1
and Cry1 in the hypothalamic Suprachiasmatic Nuclei (SCN) were also disrupted
in mice carrying tumors. Altogether, these results suggest that tumor-secreted
molecules (i.e., tumor macroenvironment) could modulate the function of the
central circadian pacemaker (SCN). This could account for the worsening of the
peripheral biological rhythms such as locomotor activity or serum
glucocorticoids. Since disruption of the circadian rhythms might accelerate
tumorigenesis, monitoring circadian patterns in cancer patients could offer a new
tool to get a better prognosis for this disease. |
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