Cancer spreads much more aggressively during sleep

Welcome to this edition of?Sleepletter?where we offer you easy-to-read insights from the latest research papers from the field of sleep neurobiology and clinical sleep medicine. We hope you enjoy the content!

Most cancer cells spread during sleep

Breast cancer affects close to 1.5 million women worldwide every year and causes almost 500 000 deaths. According to the American Cancer Society,?1 in 8 women in the United States will develop breast cancer in their lifetime. As with so many cancer types, the earlier the diagnosis, the higher likelihood of successful treatment. But, breast cancer is highly heterogeneous in its pathological characteristics, with some cases showing slow growth with excellent prognosis, while others being aggressive tumors. Around 30% of cases are diagnosed at a later stage where metastases are present, whereas this number rises to 50%-80% in low- and middle-income countries. This is a big problem, since metastatic cancer is much more difficult to treat and with poorer survival. Metastatic spread of cancer is achieved by the circulating tumor cells (CTCs) which detach from the main site of the tumor and go in the bloodstream to other areas of the body to divide and create metastatic tumors. Therefore, understanding the dynamics of CTCs at a higher level would allow us to develop therapies that would be more successful at combating them. Fortunately, a new article from Nature may have done just that.

We know that optimal sleep quality is a protective factor many disorders, including certain types of cancer. But what if I told you that researchers found that metastatic breast cancer cells are far more aggressive and active during your sleep compared to your wake period? Let’s dig deeper at what this surprising study found. Scientists led by ETH Zurich took blood samples from 30 women with different stages of breast cancer during their wake (10am) and sleep (4am). Strikingly, they found that almost 80% of all circulating tumor cells were found in blood samples obtained at 4am. Then, they confirmed that the same phenomenon is conserved in mouse models of breast cancer too, with mice having 6-88 times more CTCs during the sleep phase. Now, they could study in detail in rodents why this is happening.?

Close to 80% of all circulating tumor cells in blood samples of 30 women with breast cancer are found during sleep.

Another confirmation that this phenomenon is real came when the researchers provoked a jet-lag effect in mice and when they gave mice melatonin, a hormone that regulated the sleep-wake cycle. These mice also exhibited much higher levels of CTCs compared to controls, suggesting that metastatic spread is circadian rhythm dependent. Giving mice luzindole, a melatonin receptor antagonist, resulted in a marked decrease of CTCs.

Apart from an increased number of CTCs, are the ones produced during sleep more aggressive too? Researchers isolated 150 CTCs from wake and sleep phase and injected them into mice without tumors to measure their metastatic potential. Interestingly, the highest metastatic burden was also found during the sleep phase, and it is predominantly caused by CTCs isolated from mice with breast cancer during sleep. This is another confirmation that CTCs really are more aggressive during sleep, even in mice without cancer.

When analyzing gene expression of CTC during sleep and wake, marked differences were found. Genes responsible for cell division and mitosis are dominant during sleep, while those pertaining to making ribosomes (locations of protein synthesis) are much more active during wake. But why are CTCs more aggressive during sleep? While we don’t know this yet, results from the study suggest that key circadian rhythm-influenced hormones such are insulin, testosterone and melatonin play an important role in CTC count.

Overall, these highly surprising results provide not only new information about the dynamics of CTCs, but also raise important questions whether treatment of cancer metastasis should be done at certain parts of the day for better outcomes. Do these results suggest that sleep is bad for you? Not at all, but they do show how cancer cells behave differently depending on the time of day, and future cancer treatment trials should take advantage of this highly valuable insight.

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About the author

Alen Juginovi??is a medical doctor and postdoctoral researcher in the Department of Neurobiology at Harvard Medical School in Boston, MA, USA studying the effect of poor sleep quality on health. He is also organizing international award-winning projects such as Nobel Laureate conferences, international congresses, concerts and other, as well as participating in many events as a speaker. Feel free to contact him via LinkedIn for any inquiries.