Scientists from the University of Leeds and The Institute of Cancer Research, London, have discovered a new protein which triggers the growth of blood vessels in breast cancer tumours which have spread to the brain, a common location which breast cancer can spread to.
Dr Georgia Mavria’s team in the School of Medicine at Leeds found that by withholding the DOCK4 protein in mouse models, a particular part of the blood vessel did not form as quickly, meaning tumours grew at a slower rate.
Dr Mavria said: “We want to understand how these tumours form and grow, but we still need to do more research to stop these tumours growing altogether.
“The finding gives an important indicator of how the protein affects the growth of secondary breast tumours in the brain. The discovery could also enable experts to predict which patients might be at risk of their breast cancer spreading, and develop drugs to prevent the growth of secondary tumours.”
Working with Professor Chris Marshall, Professor of Cell Biology at The Institute of Cancer Research, London and the late Dr Tony Pawson at the Lunenfeld-Tanenbaum Research Institute in Toronto, researchers found that a complex of two related proteins, DOCK4 and DOCK9, is critical in the formation of the lumen, the interior space of a vessel through which blood flows.
By impeding the speed at which the lumen forms, tumours are not fed as effectively by blood
Normally, when breast cancer spreads to other parts of the body, it forces new blood vessels to form to supply it with nutrients and oxygen to help it to grow, resulting in tumours that are very difficult to treat.
Professor Marshall said: “Our study reveals new insights into how the complex process of forming blood vessels is controlled. This knowledge could lead to new approaches to preventing the blood supply to tumours and metastases. If we can find new ways to reduce the blood supply to tumours, we might be able to find new ways to slow cancer growth in future.”
The research, which has been published in Nature Communications, was funded by Breast Cancer Campaign, Yorkshire Cancer Research and Cancer Research UK.
Dr Matthew Lam, Senior Research Communications Officer at Breast Cancer Campaign and Breakthrough Breast Cancer, said: “These findings could one day help us better identify and treat patients that might be at risk of their breast cancer spreading to the brain, a particularly common site for metastasis.
“12,000 women have their lives cut short by breast cancer in the UK each year. An understanding of what is happening on a molecular level ”“ such as the role played by DOCK proteins ”“ will be essential if we are to find ways to prevent secondary tumours and finally stop women dying from the disease.”
Kathryn Scott, Head of Research and Innovation at Yorkshire Cancer Research, said: “Tumours need blood vessels to grow, but these blood vessels could be the cancer’s weakest link because it is believed that they are less able to become resistant to drugs than the cancer cells themselves. Targeting drugs to the blood vessels that are serving the tumour rather than the tumour itself is an exciting new area of research and we are supporting a number of projects in Yorkshire which are investigating this approach.”
Dr Aine McCarthy, Science Information Officer at Cancer Research UK, said: “This research shows for the first time that a molecule called DOCK4 is a key player in tumour blood vessel development and blocking it could slow tumour growth by starving the cancer cells. But the study was carried out in mice, so more research is needed to see if drugs can be developed that target the molecule and whether this approach would be safe and effective in people with cancer.”
Notes to Editors
- Dr Georgia Mavria is available for interview. Contact Ben Jones in the University of Leeds press office on 0113 343 8059 or email B.P.Jones@leeds.ac.uk
- A copy of the research paper, “A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis”, by Abraham et al, is available from the press office.
University of Leeds
- The University of Leeds is one of the largest higher education institutions in the UK, with more than 31,000 students from 147 different countries, and a member of the Russell Group research-intensive universities.
- We are a top 10 university for research and impact power in the UK, according to the 2014 Research Excellence Framework, and positioned as one of the top 100 best universities in the world in the 2014 QS World University Rankings. www.leeds.ac.uk
The Institute of Cancer Research
- 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
- Last updated: 01/07/2015
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