When cancer cells enter the bloodstream and travel to a new part of the body to open a store, they are most lethal – a process called metastasis. Now, one study finds that for people with breast cancer, these artificial cells – rotating tumor cells, or CTCs – are more likely to jump into the bloodstream at night than during the day.
The discovery reveals some key human physiology that is still under the radar and could lead to better ways to monitor cancer progression, says Chin-Jun Man, a chronobiologist at the University of Manchester in the United Kingdom.
The research community has been debating for decades how circadian rhythms affect cancer. The study found that “tumors awaken when patients are asleep,” said co-author Nicola Aceto, a cancer biologist at the Federal Institute of Technology in Zurich, Switzerland. It is a “step forward” in understanding metastases, he says. “And moving forward is a long-term good thing for patients.” The investigation was announced on June 22 nature1.
Cancer by the hour
In 2007, the International Agency for Research on Cancer rated circulatory rhythms as a “probable” carcinogen, and long-term studies found that people who worked part-time, such as flight attendants and night nurses, had a higher risk of developing breast cancer.two. This remains an open question as to why.
The circadian clock, controlled by various genes that represent specific molecules on a 24-hour schedule, affects many processes in the body, including metabolism and sleep. Most researchers initially thought that cancer cells were “so damaged, so mutated” and that they did not fit into such a schedule, Aceto said.
For metastasis, the first indication that this may be completely incorrect is that Aceto and his colleagues found that CTC levels in mice with tumors varied with the time of day their blood was taken. This observation led Aceto to take the blood of 30 women hospitalized with breast cancer once at 4 am and again at 10 am.
The researchers found that the bulk of the CVD found in the blood samples – almost 80% – appeared in the compartment collected at 4 am while the patients were still resting. At first, “I was surprised because dogma always releases rotating cells,” says Aceto. “But the information was very clear. Soon, we were so excited. ”
The next step for the researchers was to confirm whether this was true for several patients. To do this, the group injected breast cancer tumors into mice and tested the CTC levels of the animals throughout the day. Compared to humans, mice have an inverted circadian rhythm, meaning that they are most active at night and tend to rest during the day. The team found that the CTC levels of the animals reached a peak during the day – sometimes the concentration was 88 times higher than the baseline – and the animals were at rest.
In addition, the researchers collected CTCs from mice while the animals were resting and when they were active. They added different fluorescent tags to the two sets of cells and then injected them back into the mice. Most of the cells that developed into new tumors were cells collected while the mice were resting, indicating that CTCs were somewhat better at transmitting metastases.
Chi Van Dang, a cancer biologist at the Ludwig Cancer Research Institute in New York, says the discovery is “surprising.” Doctors measure CTC levels in the blood to help see how cancer patients are progressing – a type of fluid biopsy, so “the first lesson for me is that the day the blood sample is taken may give you incorrect information.” That means doctors want to rethink when they detect cancer, he adds.
Sleep is not the enemy
Why breast cancer cells in humans become more active at night probably depends on many factors that still need to be studied, says Aceto. Hormones, one of the tools the body uses to signal when it is time to wake up or go to sleep, may play a role. The team found that treatment of mice with hormones such as testosterone or insulin had an effect on CTC levels – lowering or increasing hormones depending on when they were given.
Understanding how this process works may one day lead to better cancer treatment, Dang says, but that fact is still far from over. He adds that more research is needed in the first place to address the complex networks that combine circadian rhythms and cancer.
At the same time, Maine warns not to think of sleep as an enemy for people with breast cancer. Some studies show that people who get cancer and sleep less than seven hours a night are more likely to die.3and circadian rhythms in mice can move cancer faster4. Research doesn’t say “you don’t need sleep or need less sleep,” he says. “It simply means that these cells prefer a certain phase of the 24-hour cycle to pass into the bloodstream.”