Research identifies on-off switch for key ‘factor’ in vascular disease and cancer

6 April 2011

Scientists at the University of Hull have identified a cellular ‘on-off’ switch that may have implications for treating cardiovascular disease and cancer.

Dr Camille EttelaieThe team has found the mechanism which controls the inclusion of a protein called tissue factor into endothelial microparticles, tiny vesicles which are released from cells in the lining of blood vessels.


< Dr Camille Ettelaie


“Although tissue factor is part of the body’s natural healing process, helping create clots to stop bleeding and repair injuries, high levels circulating in the blood stream can be harmful,” says lead researcher Dr Camille Ettelaie. “Excessive tissue factor is linked to cardiovascular disease, including the formation of irregular blood vessels and higher risk of thrombosis, leading to heart attack and stoke.”

Dr Ettelaie and co-researcher Dr Mary Collier found that two tandem amino acids within tissue factor work like an ‘on-off switch’ within the cells, controlling how and when it is incorporated into the microparticles and released. When a phosphate molecule is added to the first one of these two amino acids, the process starts and when added to the other, it stops.

By blocking the addition of the phosphate molecules to the first amino acid, the researchers were able to stop the process – opening up the possibility of controlling when and how much tissue factor is released in microparticles.

“The aim of the research was to see if there might be a way to control the output of tissue factor from endothelial cells into microparticles,” says Dr Ettelaie, “This project focused on the vascular system and is helpful in controlling thrombosis, but tissue factor is also released in microparticles from cancer cells and linked to cell proliferation – so our findings could have implications for treating cancer as well.

“Tissue factor is exploited by cancer cells – they use it to speed up their growth directly, and also increase the growth of blood capillaries which supply the tumour with nutrients – but if levels of tissue factor are too high within a cell, then the cell will die. If we could use this switch to stop cancer cells getting rid of excess tissue factor, it might be possible to kill them without causing detrimental effect to the body’s normal cells.”

The findings from the research – which was partly funded by Yorkshire Cancer Research and the Castle Hill Hospital Cancer Trust Fund – are published in the latest issue of Journal of Biological Chemistry (April 8).

Ends.


Page last updated by Andrea Luquesi on 4/11/2011

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More information

About Dr Camille Ettelaie
Dr Camille Ettelaie is a lecturer in biomedical sciences in the Department of Biology at the University of Hull. Her research focuses on tissue factor, particularly its role in cardiovascular disease and cancer.

About health research at the University of Hull
Health-related research at the University of Hull ranges from biology and biochemistry to sports science, psychology and medicine. The University heads major UK and EU clinical trials into heart disease, dementia care, obesity and nutrition and is a recognised centre for research into head and neck cancers, medical imaging, respiratory diseases and remote monitoring of health conditions (telehealth).

Health research at the University of Hull is highly translational, with strong links between fundamental scientists and clinicians ensuring maximum impact on treatment and practice. The University has a joint medical school with the University of York – Hull York Medical School (HYMS) – which works closely with regional NHS trusts and trains 130 new doctors each year.

In the 2008 national Research Assessment Exercise (RAE), 80% of the University’s research across all fields was judged to be of international standard in terms of originality, significance and rigour. The National Student Survey (NSS) consistently ranks the University in the top ten mainstream English Universities.

About Yorkshire Cancer Research
Harrogate-based Yorkshire Cancer Research (YCR), the UK’s largest regional medical research charity, funds around £7m a year of internationally recognised cancer research at its five centres of excellence at the universities of Bradford, Hull, Leeds, Sheffield and York and their associated teaching hospitals.

The charity’s 200 plus scientists and clinicians are among the world leaders in the fight against cancer and the charity has committed a further £15 million over the next few years to continue funding them in its effort to find cures for all forms of cancer.

Yorkshire Cancer Research also funds a range of commercial and clinical projects across the region which aim to get tomorrow’s cancer drugs and new treatments to the bedside, directly benefitting cancer patients. Yorkshire Cancer Research is the most cost efficient cancer research charity in the UK spending 83 pence in every pound on cancer research. Over the next 10 years, it is committed to slashing current statistics that show 259 people die every week from cancer in Yorkshire alone.

Registered charity number 516898.