The cells responsible for the spread of cancer and for most deaths from cancer — may have a fatal weakness according to
studies in mice: a reliance on certain fats to fuel their invasion.
It is a difficult and hazardous
undertaking for a cancer cell to uproot itself, travel through the bloodstream
and take hold in an entirely different part of the body. (Non-cancerous cells
are often programmed to self-destruct if they leave the tissue they live in.)
Researchers have long struggled to understand which cancer cells can manage the
feat, and how they do so.
But a study published on 7 December
in Nature has identified a population of oral tumor cells that are
able to make the journey in mice, and has found that such cells may feast on
fats to fuel the trip. Determining how certain cancer cells spread throughout
the body — a process called metastasis — is a big step forward, says Xiang
Zhang, a cancer researcher at Baylor College of Medicine in Houston, Texas, who
was not involved in the study. “Now people have a suspect they can follow.”
To find that suspect, Salvador
Aznar Benitah of the Institute for Research in Biomedicine at the Barcelona
Institute of Science and Technology in Spain and his colleagues looked among
oral-cancer cells for those that could seed tumors. Within that population of
cells, the team found some that expressed high levels of a molecule called
CD36, which helps cells to take up lipids from their environment.
Stopping the spread
Benitah and his team found that
high CD36 expression was required for metastasis in mice. Antibodies that
blocked CD36 — and eliminated its interaction with fatty acids — completely
inhibited metastasis, although they did not affect the development of primary
tumors.
The researchers also mined public
databases and found that high expression of CD36 correlated with poor medical
outcomes in bladder, lung, breast and other cancers in people.
Benitah’s team is now working to
develop antibodies against CD36 that could be used in clinical trials, although
he estimates it would take at least another four years to reach that milestone.
Benitah notes that such a therapy may be effective even after cancer has
started to spread: in mice, experimental antibodies eradicated metastatic
tumors 15% of the time. The remaining metastatic tumors shrunk by at least 80%.
The team is also looking at the
implications of another finding: feeding the mice a high-fat diet led to more
and larger tumors in the lymph nodes and lungs — a sign of metastasis —
compared with mice on normal diets.
They went on to test a specific
saturated fatty acid called palmitic acid -- a major component of animal and
vegetable fats and present at high levels in palm oil which is used in many
house hold products from peanut butter and processed food to toothpaste. The
researchers treated human oral tumours with palmitic acid for two days then
injected them into mice fed a standard diet. The team observed that all the
mice with CD36 developed cancer spread compared to only half when not treated
with palmitic acid.
Benitah’s team is now carrying out
a study that aims to enroll 1,000 people with cancer, profiling lipids in their
blood to look for any links to the spread of cancer cells.
Journal Reference:
Gloria Pascual, Alexandra
Avgustinova, Stefania Mejetta, Mercè Martín, Andrés Castellanos, Camille
Stephan-Otto Attolini, Antoni Berenguer, Neus Prats, Agustí Toll, Juan Antonio
Hueto, Coro Bescós, Luciano Di Croce, Salvador Aznar Benitah. Targeting
metastasis-initiating cells through the fatty acid receptor CD36. Nature,
2016
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