Sunday, 4 Jun 2023

Prostate tumours ‘spit out a protein that activates cancer cells’

Cancer spreads when cells SPIT OUT a protein: Hope for new treatments as scientists discover how tumours grow bigger

  • Tiny pieces of the protein EN2 are taken up by other cancerous cells
  • This activates cells, causes them to change shape or makes them fuse together
  • EN2 also helps cancerous cells ‘hide’ from the immune system 
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Prostate tumours may spread by ‘spitting out’ a protein that ‘activates’ dormant cancerous cells, a study suggests.

Scientists found tiny pieces of a protein, called EN2, are taken up by other cancerous cells, causing them to change shape or fuse together.

Fused cancer cells are thought to be a sign of aggressive cancer that is better at spreading and surviving chemotherapy.

Taking up EN2 also causes cells to express a gene that helps to hide tumours from the immune system, the ‘very significant’ research found. 

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Prostate tumours may spread by ‘spitting’ a protein that ‘activates’ cancerous cells (stock)

The University of Bradford researchers hope blocking EN2 will lead to more effective treatments for cancer.

The study was conducted on prostate tumours. Existing drugs for prostate cancer can cause erectile dysfunction or urinary incontinence.

Professor Richard Morgan, study author, said: ‘For tumours to survive, grow bigger and spread they need to control the behaviour of cancer cells and the normal cells around them and we’ve found a means by which they do this.

‘Blocking this process could be a potential target for future cancer therapy.’

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Around 50,000 men in the UK are diagnosed with prostate cancer each year, data from Cancer Research UK shows.

And in the US, around 174,650 men are diagnosed every year, American Cancer Society statistics reveal. 

EN2 has previously been found to play a role in early brain development, as well as being present in high amounts in many types of cancers. 

To determine the part it plays in prostate cancer, the researchers tagged the protein with a fluorescent green marker in the laboratory.

They then studied how it interacts with both cancerous and normal cells in a human prostate model.

Results revealed both cell types fuse with vesicles carrying EN2 and then take the protein up.

To examine how this occurs in finer detail, the researchers carried out time-lapse photography, where pictures were taken of the cells every five minutes for 24 hours.

It showed the cells eject EN2, which is then taken up by dormant cancer cells, causing them to become activated, change shape or fuse together. 

The cells then generate another EN2-containing vesicle that they too can expel. 

‘We think this is significant because cell fusion in cancer is relatively unusual and is associated with very aggressive disease,’ Professor Morgan said.

‘It can lead to new and unpredictable hybrid cells that are frequently better at spreading to different sites, and surviving chemotherapy and radiotherapy.’ 

Further analysis revealed that when normal cancer cells take up EN2, they express a gene called MX2.

This generates an anti-viral response that may help tumours . 

‘We believe the cancer is trying to minimise the chances of the cells around it being infected by a virus, to avoid scrutiny by the immune system,’ Professor Morgan said.

‘This could undermine the effectiveness of immunotherapy treatments, which try to use viruses to kill cancer by stimulating the immune system to attack it.’

The researchers were surprised to find EN2 was expressed in the cell membrane rather than just it’s nucleus, which acts like a brain.

They believe this will give scientists greater opportunity to block EN2’s action by targeting a part of the protein expressed on the cell’s surface. 

Study author Hardev Pandha, professor of medical oncology at the University of Surrey, added: ‘This work follows on from earlier studies at Surrey where detection of EN2 in urine, after secretion from prostate cancer cells, was shown to be a robust diagnostic biomarker of prostate cancer. 

‘The more we learn about prostate cancer the more that can be done to identify and treat this devastating disease.’ 


How many people does it kill?

Prostate cancer became a bigger killer than breast cancer for the first time, official statistics revealed earlier this year. 

More than 11,800 men a year – or one every 45 minutes – are now killed by the disease in Britain, compared with about 11,400 women dying of breast cancer.

It means prostate cancer is behind only lung and bowel in terms of how many people it kills in Britain. In the US, the disease kills 26,000 each year.

Despite this, it receives less than half the research funding of breast cancer – while treatments for the disease are trailing at least a decade behind.

How quickly does it develop? 

Prostate cancer usually develops slowly, so there may be no signs someone has it for many years, according to the NHS. 

If the cancer is at an early stage and not causing symptoms, a policy of ‘watchful waiting’ or ‘active surveillance’ may be adopted. 

Some patients can be cured if the disease is treated in the early stages.

But if it diagnosed at a later stage, when it has spread, then it becomes terminal and treatment revolves around relieving symptoms.

Thousands of men are put off seeking a diagnosis because of the known side effects from treatment, including erectile dysfunction.

Tests and treatment

Tests for prostate cancer are haphazard, with accurate tools only just beginning to emerge. 

There is no national prostate screening programme as for years the tests have been too inaccurate.

Doctors struggle to distinguish between aggressive and less serious tumours, making it hard to decide on treatment.

Men over 50 are eligible for a ‘PSA’ blood test which gives doctors a rough idea of whether a patient is at risk.

But it is unreliable. Patients who get a positive result are usually given a biopsy which is also not foolproof. 

Scientists are unsure as to what causes prostate cancer, but age, obesity and a lack of exercise are known risks. 

Anyone with any concerns can speak to Prostate Cancer UK’s specialist nurses on 0800 074 8383 or visit

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