Cancer cells can metastasize faster while patients are sleeping

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Cancer cells can metastasize faster while patients are sleeping

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Cancer cells can metastasize faster while patients are sleeping.

Some scientists stay up late to carry out experiments, while others start work early in the morning.

Then the same experimental steps, only the sampling time is different, may the results be different?

This is what happened to some researchers at the Federal Institute of Technology in Zurich (ETH): When testing blood samples from mice with tumors, researchers who took samples in the morning and at night always had different results, especially in the circulation in the blood. Cancer cell levels vary widely.

These circulating cancer cells are strays sloughed off from the carcinoma-in-situ area and search for suitable new habitats throughout the body.

In the latest study, published in Nature, the research team determined in breast cancer patient samples and mouse models that the metastasis of cancer cells was unexpectedly closely related to sleep and specific hormone levels.

Metastasis of cancer cells often heralds things getting tougher, and makes cancer treatment a lot harder. But if we want to stop this process, we have to understand how it happens.

Now, a collaboration between ETH and the University of Basel in Switzerland has finally identified a cunning way for cancer to metastasize: ” When cancer patients fall asleep, cancer cells wake up. “

The research team recruited a total of 30 female volunteers with breast cancer who were either untreated or temporarily discontinued. The research team then collected their blood samples at 10 a.m. (awake) and 4 a.m. (sleeping).

Although some of these patients were in the early non-metastatic stage and some were already metastatic, they showed the same phenomenon: the majority of circulating cancer cells (CTCs), the CTC population, were derived from samples obtained at night.

More circulating cancer cells appeared in sleep samples from female breast cancer patients (Image source: Reference [2])

With this finding, the researchers believe that the circadian rhythm is likely to affect the process of cancer metastasis.

So the researchers designed a batch of tumor mouse models of breast cancer and began to conduct deeper analysis.

Intuitively, mice, in contrast to humans, had more CTCs in daytime samples.

But it is precisely because the habit of mice is nocturnal that there is a contrast in daytime sleep, and the essence is still that the CTC will be higher during sleep.

Of course, mice experiments have the advantage of being able to forcibly disrupt their rhythm clocks, confusing the timing of their rest and activity.

After some time, they reanalyzed the blood samples for CTC levels. The results were very obvious. Compared with normal mice, the number of single CTCs in the rhythm disordered mice was reduced to 1/38~1/282, and the CTC group was also reduced to 1/63~1/484.

Amazingly, there was almost no difference in the size of the in situ tumors between these mice, the difference was the number of these free CTCs.

Even when the mice’s rhythms were disrupted, they still had circulating cancer cells that rose when they were at rest and dropped when they were active (Image credit: Reference [2])

Since circadian rhythm affects tumor migration, is there a relationship between rhythm-related hormones? For example, does sleep-related melatonin also play a role?

The researchers tried artificially boosting melatonin levels in mice, and regardless of whether the mice had a normal or chaotic rhythm, they got a lot of melatonin 2 hours before a break.

After about 3 weeks, the researchers could clearly observe that melatonin significantly increased the number of individual CTCs and CTC groups in the blood of the mice.

But if a melatonin receptor inhibitor is added, CTCs in the blood drop in reverse. But no matter how the circulating cancer cells changed, the volume of the in situ tumor remained unchanged.

“It can be determined that the process of CTC detachment and escape from the in situ tumor is controlled by hormones such as melatonin, which in turn affects the circadian rhythm,” said Zoi Diamantopoulou, Ph.D., lead author of the study.

He and his colleagues also finally came to this surprising conclusion: the cells that would later form cancer metastases really emerged and became active during sleep.

In the investigators’ view, this finding suggests that future studies of tumors are likely to record the timing of biopsy samples so that the data can be compared.

In the future, they want to determine whether other cancer cell types, besides breast cancer, have the same pattern.

How to make this discovery help optimize existing cancer treatments is also one of the key directions for future research.

References:

[1] Breast cancer spreads at night. Retrieved June 22, 2022 from https://www.eurekalert.org/news-releases/956526?

[2] The metastatic spread of breast cancer accelerates during sleep. Nature (2022). DOI: 10.1038/s41586-022-04875-y

Original title: “Nature” found that when people sleep, cancer wakes up! Cancer cells metastasize faster while sleeping

Cancer cells can metastasize faster while patients are sleeping.

(source:internet, reference only)

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