Breast cancer metastases form primarily during sleep

Breast cancer spreads mainly in sleep. This is stated by a research group led by cell biologist Zoi Diamantopoulou of ETH Zurich in the journal Nature. In doing so, the cells separate from the original tumor, enter the bloodstream and form metastases elsewhere. Until now, these circulating tumor cells (CTCs) have been thought to form continuously or in response to mechanical stimuli such as surgery.

The team took a blood sample from 30 breast cancer patients twice: at 4 am (sleep phase) and at 10 am (waking phase). It was found that almost 80 percent of the total CTC came from a nocturnal blood sample.

To examine this surprising finding in more detail, the researchers examined mice that had either been genetically modified to develop breast cancer or that had been injected with human breast cancer cells. In rodents, too, CTCs formed primarily during sleep – but during the day because the mice are nocturnal. If the researchers left the animals awake longer, significantly fewer circulating tumor cells formed during the day.

In contrast, melatonin administration led to more tumor cells in the bloodstream. The hormone regulates the sleep-wake cycle and has a sleep-inducing effect. In genetically modified mice without a functioning circadian rhythm, CTCs developed independently of the rest period.

The authors also injected resting and active CTC into healthy tumor-free mice at various stages of the circadian cycle. They found that resting phase cells formed more aggressive tumors than active phase cells. In addition, resting mice were more likely to develop tumors than active animals.

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