Researchers discover cell communication mechanism that drives cancer adaptation

Date:
July 28, 2020
Source:
University of Oxford
Summary:
Researchers have uncovered a new mechanism by which cancer cells
adapt to the stresses they encounter as they grow and respond
to therapies.



FULL STORY ========================================================================== Collaborative Cancer Research UK-funded studies from University of
Oxford researchers have uncovered a new mechanism by which cancer
cells adapt to the stresses they encounter as they grow and respond
to therapies. This mechanism involves cells releasing small vesicles,
known as exosomes. These contain complex mixtures of proteins, RNAs and
other molecules, which can re-programme surrounding cells. Exosomes are
thought to be released by all cells within the body, and play important
roles in many processes in healthy individuals such as immunity and reproduction. But, in cancer they can turn bad and drive pathological
changes such as tumour growth and metastasis.


==========================================================================
Up until now, research has suggested that exosomes are made in
compartments in cells known as late endosomes, which are also used to
keep cells healthy by clearing out damaged proteins and structures in
the cell. By combining complementary analysis in fruit flies and human
cancer cells, the collaborative teams have shown that exosomes are also
made in the cell's recycling system, which diverts reusable proteins
away from the waste disposal system. They are called Rab11a-exosomes
and carry a different set of cargos that may help cancers to grow and
survive current treatments.

As a tumour grows bigger, the cells within it are starved of key nutrients
such as amino acids, and these stressed cells produce Rab11a-exosomes
loaded with molecules made by the cancer cells. According to Associate Professor Deborah Goberdhan, who led the research: "These 'bad exosomes'
can then give other cells around them a growth-promoting boost and
can potentially lead to selection of more aggressive cell types and a
worse outcome. The production of Rab11a-exosomes may explain why some
patients don't respond to certain treatments and why others frequently
develop resistance to therapies." "It's becoming increasingly clear
that anti-cancer therapies that block growth may need to be given in combination with drugs that prevent tumour cells adapting to the therapy,
and reducing the production of these exosomes might be one important way
to do this." "A key step will be to work out how the bad exosomes that
drive cancer progression are made, so that therapies can be designed to
block them. This is likely to take some time. However, developing ways
to detect these exosomes in patient blood is an important shorter-term
goal. Such an approach might detect cancer at early stages or predict
how patients will respond to drugs, both of which could have a major
impact on cancer survival and the design of more personalised treatments
for patients." Dr Emily Farthing, Senior Research Information Manager
at Cancer Research UK said: "This exciting research has discovered
that exosomes can act in a way we weren't previously aware of, which
could be helping tumours to grow and become resistant to anti-cancer treatments. This lab-based work is still a long way off benefitting
people with cancer, but provides helpful clues to how we might be able
to tackle the disease in new ways in future." The newly published
research has already attracted further funding to start screening for
these alternative exosomes in patients, and a major current focus of
the team is to identify ways of blocking their production, so that their
role in cancer pathology can be fully assessed.

Professor Goberdhan said: "By continuing to combine analysis in human
cancer cell lines and flies, we have started to highlight genetic
manipulations that appear to specifically block the production of Rab11a-exosomes, which we are now following up."

========================================================================== Story Source: Materials provided by University_of_Oxford. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Shih‐Jung Fan, Benjamin Kroeger, Pauline P Marie, Esther
M Bridges,
John D Mason, Kristie McCormick, Christos E Zois, Helen Sheldon,
Nasullah Khalid Alham, Errin Johnson, Matthew Ellis, Maria Irina
Stefana, Cla'udia C Mendes, Stephen Mark Wainwright, Christopher
Cunningham, Freddie C Hamdy, John F Morris, Adrian L Harris,
Clive Wilson, Deborah CI Goberdhan. Glutamine deprivation alters
the origin and function of cancer cell exosomes. The EMBO Journal,
2020; DOI: 10.15252/embj.2019103009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200728113546.htm

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