Prostate cancer cells change the behaviour of other cells around them,
including normal cells, by 'spitting out' a protein from their nucleus, new
research has found.
The tiny pieces of protein are taken up by the other cells, provoking
changes that promote tumour growth and -- the researchers believe -- help the
cancer hide from the body's immune system.
The process has been captured for the first time on video by researchers at
the University of Bradford and University of Surrey. The research is published
today [26 March] in Scientific Reports.
Lead researcher, Professor Richard Morgan from the University of
Bradford, 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."
The research focused on a protein called EN2 that has a role in early
development of the brain but has also been found at high levels in many types
of cancer cells.
The team highlighted the protein using a green florescent tag. The
researchers then studied its activity in human prostate cancer cells, normal
prostate cells and in bladder cancer, melanoma and leukaemia cells. They found
that both cancer and normal cells took up the protein from other cells.
They also did time lapse photography of prostate cancer cells, taking
pictures every five minutes for 24 hours. The resulting video shows the cells
eject small parts of themselves containing the green florescent protein that
are then taken up by otherwise dormant cancer cells, causing them to
reactivate, changing shape or fusing together.
Professor Morgan explains: "We think this is significant because
cell fusion in cancer is relatively unusual and is associated with very
aggressive disease. It can lead to new and unpredictable hybrid cells that are
frequently better at spreading to different sites and surviving chemotherapy
and radiotherapy."
Molecular analysis of the normal prostate cells showed that take up of
EN2 caused them to express a gene called MX2 that generates an anti-viral
response.
"We believe the cancer is trying to minimise the chances of the
cells around it infected by a virus, to avoid scrutiny by the immune
system," says Professor Morgan.
"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 also surprised to find the EN2 protein in the cell
membrane as well as in the nucleus -- which is very unusual for this type of
protein. This provides an opportunity to block its action, and the team were
able to identify that part of the protein that was accessible at the cell
surface to be a potential target for treatment.
Hardev Pandha, Professor of Medical Oncology at the University of
Surrey, says: "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."
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