Better understand breast cancer metastases
Cancer is deadliest when tumor cells spread through the blood throughout the body. It has now been discovered that this process, known as metastasis, occurs more frequently in breast cancer at night. The new findings highlight how the body’s circadian rhythm affects cancer.
A recent study involving experts from the University of Manchester looked at how the circadian rhythm affects the spread of circulating tumor cells. The results were published in the journal Nature.
Breast cancer due to irregular working hours
As early as 2007, the International Agency for Research on Cancer classified a disturbed circadian rhythm as a probable carcinogen. At the time, experts attributed this to the fact that long-term studies had shown that people with irregular working hours (eg flight attendants) were more likely to develop breast cancer.
What is the internal clock?
The so-called internal human clock, known in technical terms as the circadian rhythm, is controlled by various genes, which express certain molecules according to a 24-hour schedule.
The circadian rhythm influences many processes that take place in the human body, including metabolism and sleep. Until now, however, many researchers have assumed that cancer cells have mutated too much to be affected by the circadian rhythm.
How the body’s circadian rhythm influences cancer has been a topic of debate in the scientific community for decades. The researchers found the first indications that metastasis may well be influenced by the internal clock in mice.
Effect of time of day on circulating tumor cells
In animals with tumors, blood tests showed that the amount of circulating tumor cells varied depending on the time of day. This observation prompted the research group to draw blood from 30 women with breast cancer once at 4 a.m. and a second time at 10 a.m.
More circulating tumor cells in resting sample
The team found that the majority of circulating tumor cells detected in the blood samples (nearly 80%) were present in the sample taken at 4 a.m. “At first, I was surprised, because the dogma says that tumors constantly emit circulating cells,” reports study author Nicola Aceto.
Next, the researchers then transplanted cancerous breast tumors into mice and looked at the animals’ levels of circulating tumor cells throughout the day. Compared to humans, mice have an inverse circadian rhythm, being more active at night and resting during the day.
Experts found that concentrations of circulating tumor cells in animals were highest during the day (during the resting phase), in some cases even up to 88 times higher than the initial concentration.
The team also collected circulating tumor cells from the mice. This happened both when the animals were resting and when they were active. The two sets of cells were labeled with different fluorescent markers and then injected back into the mice.
Most of the cells that grew into new tumors were cells collected while the mice were resting, the team reports. This suggests that these circulating tumor cells are better able to metastasize for some reason.
Skewed test results in practice
The level of circulating tumor cells in the blood (a type of liquid biopsy) is also used by professionals to determine cancer progression. Therefore, according to study author Chi Van Dang, it is important to recognize that the time at which a blood sample is taken can provide misleading information.
“Why human breast cancer cells are more active at night likely depends on a variety of factors that have yet to be investigated,” adds study author Aceto. Special hormones could play a role here, with which the body signals, among other things, when it is time to wake up or go to bed.
When mice were treated with hormones such as testosterone or insulin, levels of circulating tumor cells either decreased or increased depending on when the hormones were administered, the research team reports.
Better cancer treatment on the horizon
Further studies are now needed to unravel the complex web between circadian rhythms and cancer. But understanding the process by which circadian rhythms affect metastasis could one day lead to better cancer treatments, Dang points out.
Sufficient sleep is also important for cancer patients
Nor should people with cancer begin to view sleep negatively in relation to their disease, say the researchers. Some studies have already shown that people with cancer who sleep less than seven hours a night have a higher risk of premature death.
Additionally, research has shown that disrupting circadian rhythms in mice contributes to faster cancer progression. It is therefore not recommended to break your own rhythm and sleep as little as possible.
However, the new study showed that circulating tumor cells prefer a certain phase of the 24-hour cycle to enter the bloodstream, adds study author Qing-Jun Meng. (as)
Author and source information
This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Freda Kreier: These cancer cells wake up when people sleep; in: Nature (published on 06/22/2022), Nature
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.