Researchers say breast cancer cells are more likely to jump into the blood when people are resting.
Cancer is most deadly when cells from a tumor enter the bloodstream and travel to a new location in the body to settle. This is a process called metastasis. Now, a study finds that for people with breast cancer, these stray cells, called circulating cancer cells, or CTCs, are more likely to jump into the blood at night than during the day!
This discovery reveals some basic human physiology that has not been understood until now and could lead to better ways of monitoring the progression of cancer, says Qing-Jun Menga chronobiologist at the University of Manchester, UK.
The research community has been debating for decades how the body’s circadian rhythms affects cancer. With this study, it became clear that “tumors wake up when patients sleep,” says Dr Nicola Aceto, a cancer biologist at the Swiss Federal Institute of Technology in Zurich, Switzerland. This is a “step forward” in understanding metastasis, he notes. “And the steps forward are a good thing for patients in the long run.” The research was published June 22 in Nature.
In 2007, the International Agency for Research on Cancer classified circadian rhythm disruption as a “probable” carcinogen, after long-term studies concluded that people who work odd hours such as flight attendants and night nurses are at greater risk of developing lung cancer. breast2. “Why” this happens remains a mystery.
A person’s circadian clock affects many processes in the body such as metabolism and sleep. Most researchers, however, had initially assumed that cancer cells were so confused, so mutated, that they would not adhere to such a timetable.
As for metastases, the first hint that this might not be entirely true came when Aceto and his colleagues noticed that the levels of CTCs in tumor-bearing mice varied by time of day. This observation led the researcher to collect blood from 30 women being treated for breast cancer, once at 4 am. and another one at 10 am..
The researchers found that the bulk of the CTCs they detected in the blood samples—nearly 80 percent—appeared in the portion collected at 4 a.m., when the patients were still resting. At the beginning, “I was surprised because the dogma is that tumors send out circulating cells all the time,” says Aceto. “But the data was very clear. So, right after our surprise, we started to get really excited».
The next step for researchers was to confirm whether this was true beyond these few people. To do this, the team “grafted” breast cancer tumors into mice and looked at the animals’ CTC levels throughout the day. Compared to humans, mice have an inverted circadian rhythm, meaning they are more active at night and tend to rest during the day. The team found that the animals’ CTC levels peaked during the day, sometimes at a concentration that was up to 88 times higher than the baseline value, when the animals were at rest.
In addition, the researchers collected CTCs from the mice both when the animals were resting and when they were active. Most of the cells that grew into new tumors were those collected when the mice were resting, suggesting that these CTCs are somehow better at metastasizing.
This revelation is “impressive,” says Chi Van Dang, a cancer biologist at the Ludwig Institute for Cancer Research in New York. “The first lesson for me is that the time of day you take a blood sample can give you misleading information“, he says himself.
Sleep is not the enemy
The reason why human breast cancer cells are more active at night likely depends on a number of factors that have yet to be explored, Aceto says. Hormones, which are a tool the body uses to signal that it’s time to wake up or go to sleep, may play a role. The team found that treating mice with hormones such as testosterone or insulin had an impact on CTC levels, decreasing or increasing them, depending on when the hormones were administered. “Understanding how this process works could one day lead to better cancer treatments”, report the researchers, but this reality is probably still a long way off. More studies are needed first to unravel the complex tangle linking circadian rhythms and cancers.
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