When people with metastatic breast Cancer they close their eyes at night, their cancer wakes up and begins to spread.
This is a striking finding from an article published in Nature this week that negates the assumption that breast cancer metastases occur at the same rate day and night.
The result could change the way doctors collect blood samples from people with cancer in the future, the researchers say.
“In our view, these findings may indicate the need for health professionals to systematically record the time at which they perform a biopsy,” says senior author Nicola Acetoprofessor of molecular oncology at ETH in Zurich.
“It could help make the data truly comparable.”
The researchers first came across this topic when they noticed an unexplained difference in the number of circulating tumor cells in the samples analyzed at different times of the day.
“Some of my colleagues work early in the morning or late in the evening; sometimes they will also analyze blood at unusual times,” says Aceto.
Mice that seemed to have a much higher number of circulating cancer cells than humans gave another clue: mice sleep during the day when blood samples are most often taken.
To investigate what was happening, Swiss researchers studied 30 women with breast cancer (21 patients with early non-metastatic breast cancer and nine patients with stage IV metastatic disease).
They found a “striking and unexpected pattern”: most circulating tumor cells (78.3 percent) were found in blood samples taken at night, while a much smaller amount was found in samples during the day.
When the researchers injected the mice with breast cancer cells and took blood samples throughout the day, they found the same result. Circulating tumor cells were much larger when the mouse was at rest.
Interestingly, cancer cells collected during the dormant period were “very prone to metastasis, whereas circulating tumor cells formed during the active phase do not have metastatic capacity,” the researchers said.
Genetic analysis revealed that tumor cells taken from mice and resting humans increased mitotic gene expression. This makes them better at metastasizing because mitotic genes control cell division.
The researchers conducted experiments in which they gave some mice a jet stop by changing the light-dark routine. Disorder with circadian rhythm led to a massive decrease in the concentration of circulating tumor cells in mice.
In another experiment, the researchers tested whether giving mice hormones similar to those found in the body when mice were awake would affect the number of circulating tumor cells when the mouse was at rest.
The researchers found a “marked decrease” in the number of circulating tumor cells in a blood sample taken during the rest period (when the tumor would otherwise be most aggressive).
“Our research shows that the escape of circulating cancer cells from the original tumor is controlled by hormones such as melatonin, which determine our day and night rhythms,” says Zoe Diamantopoulouthe first author of the study and researcher of molecular oncology at ETH Zurich.
This paper was published in Nature.
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