Cancer cells turn healthy cells to the ‘dark side’

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Cancer cells use a mutant gene to coerce neighbouring healthy tissue into helping with the disease's growth and spread, a major new study reports.

Healthy cells are persuaded to release unique growth signals which cancer cells can use to multiply but cannot secrete themselves, researchers found.

Their study sheds light on how cancer cells and normal cells communicate with each other, and could open up new approaches to cancer treatment.

The research is published in the prestigious journal Cell today (Thursday), and was funded by the Wellcome Trust, Cancer Research UK and the Rosetrees Trust.

Scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute based at The University of Manchester found that faulty versions of the KRAS gene – often mutated in cancer – can have an important effect on healthy tissue.

Normal KRAS makes occasional signals that tell a cell to divide, but when mutated the gene becomes hyperactive and helps drive cancer cells' rapid and uncontrolled growth.

In the new study, researchers found that mutated KRAS also plays an important role in turning healthy 'stromal cells' into cancer's allies.

The study showed for the first time that there is a communication loop with a cancer-causing gene controlling cancer via healthy stromal cells.

The researchers studied communication networks in cells from a type of pancreatic cancer called pancreatic ductal adenocarcinoma – one of the most deadly forms of cancer responsible for around 9,000 deaths each year in the UK.

KRAS is mutated in more than 90 per cent of pancreatic cancer, and in nearly 20 per cent of all cancers.

The team studied thousands of different growth factors, proteins, and receptors across different pancreatic ductal adenocarcinoma cells to see how signals were being transmitted. They recognised well known pathways that KRAS uses to communicate with neighboring healthy cells but also noticed something unusual. By monitoring proteins in the two cells at the same time, they discovered that healthy cells were responding with a totally new message – a message that doubled the capacity for KRAS to drive malignant behavior in the cancer cells.

Study author Dr Chris Tape, Sir Henry Wellcome Research Fellow at The Institute of Cancer Research, London, said: "What our research underlines is that cancer cells do not drive the growth and spread of tumours alone – they can bully their healthy neighbours into helping them. Some pancreatic tumours have more healthy stromal cells within them than they do cancer cells, so understanding how cancer cells turn their neighbours into allies is critically important. We have discovered exactly how cancer cells can persuade stromal tissue to secrete key growth signals, and in doing so opened up exciting new possibilities for treatment."

Dr Claus Jorgensen, who led the research at The Institute of Cancer Research, London, and is now a junior group leader at the Cancer Research UK Manchester Institute, The University of Manchester said: "We now know that tumours are a complex mix of genetically diverse cancer cells and multiple types of healthy cells, all communicating with each other via an intricate web of interactions. Untangling this web, and decoding individual signals, is vital to identify which of the multitude of communications are most important for controlling tumour growth and spread. We have identified a key role played by the most commonly mutated gene in cancer in communicating with healthy cells. Blocking its effects could be an effective cancer treatment."

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Notes to editors

For more information contact Henry French on 020 7153 5582 or [email protected] For enquiries out of hours, please call 07595 963 613.

The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk

Cancer Research UK Manchester Institute

The Cancer Research UK Manchester Institute is a research institute within The University of Manchester, and is one of five research institutes core-funded by Cancer Research UK (CRUK). Research at the Institute spans the whole spectrum of cancer research, from programmes investigating the molecular and cellular basis of cancer to those focused on translational research and the development of novel therapeutic approaches.

About The University of Manchester

The University of Manchester, a member of the prestigious Russell Group, is the UK's largest single-site university with 38,600 students. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering, multi-disciplinary teaching and research of worldwide significance. The University is one of the country's major research institutions, rated fifth in the UK in terms of 'research power' (REF 2014), and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of just over £1 billion in 2014/15. Visit http://www.manchester.ac.uk for further information.

Cancer is one of The University of Manchester's research beacons – examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.

http://www.manchester.ac.uk/research/beacons/cancer/

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About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to improving health. We support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine.

Our investment portfolio gives us the independence to support such transformative work as the sequencing and understanding of the human genome, research that established front-line drugs for malaria, and Wellcome Collection, our free venue for the incurably curious that explores medicine, life and art. http://www.wellcome.ac.uk

About Cancer Research UK

  • Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
  • Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
  • Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated.
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that 3 in 4 people will survive their cancer for at least 10 years within the next 20 years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.

For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit http://www.cancerresearchuk.org. Follow us on Twitter and Facebook

Media Contact

Henry French
[email protected]
020-715-35582
@ICR_London

http://www.icr.ac.uk

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