Research identifies on-off switch for key ‘factor’ in vascular
disease and cancer
Last updated on 2/2/2015 Print this page
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.
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).