Stress remodels lymphatic system to help cancer spread

A cancer diagnosis is undoubtedly stressful. But for the patient, that stress itself can make the bad news worse.

Australian scientists discovered that in mice, stress remodels drainage vessels around a tumour, forming “highways” for metastatic cancer cells.

But this was reduced following treatment with a common blood pressure drug. The findings could change treatment strategies for cancer patients.

Clinical studies have shown that stressful events can worsen the survival rate of cancer patients. In mice, chronic stress promotes the spread of tumours. But exactly how stress eases cancer’s passage has been unclear.

In this study, the scientists investigated how stress affects the lymphatic system – the body’s sewerage pipe system, which drains waste such as fluid or dead cells from tissues.

The team imaged the growth of lymphatic vessels around breast cancer tumours in mice. They stressed some of the mice by locking them in a cage to stop them moving around freely for two hours a day over 21 days.

The researcher discovered that stress hormones remodelled the architecture of the lymphatic vessels around the tumours – more vessels grew and were wider, allowing more liquid to flow. This remodelled network also let cancer cells spread to lymph nodes more easily.

“We found that chronic stress signals the sympathetic nervous system – better known as the ‘fight-or-flight’ response – to profoundly impact lymphatic function and the spread of cancer cells,” study author Caroline Le from Melbourne’s Monash University explained.

But there’s good news.

The researchers blocked the mice’s response to stress hormones with a common blood pressure “beta-blocker” drug called propranolol. When they stressed mice, they found the drug reduced the lymphatic remodelling, as well as the spread of metastatic cancer cells.

And looks like it’s not just relevant to mice.

To investigate whether beta-blockers could hold hope for human cancer patients, the authors analysed clinical data from 956 breast cancer patients.

Sure enough, beta-blocker use significantly reduced the risk of metastasis to the lymph node. During a 78-month follow-up period after cancer diagnosis, 47 lymph node metastases were identified in patients not taking beta-blockers, where only one was diagnosed in those taking the medication.

“Blocking the effects of stress to prevent cancer spread through lymphatic routes may provide a way to improve outcomes for patients with cancer,” said Le.

A pilot study on breast cancer patients is currently underway, the authors told the ABC.

The study was published in Nature Communications.