Collagen can suppress growth of cancer
5 September 2013
Collagen, the most abundant protein in the human body, triggers
chemical signals that help prevent the growth of cancer, according
to a new study by the Institute of Cancer Research, London.
Boosting the collagen signals could act as an effective treatment
for cancers that grow in the presence of collagen, including
squamous cell lung cancer, for which no targeted treatments
The findings also suggest that switching off these chemical
signals, as some treatments for leukaemia do, is likely to be
counter-productive in cancers where interaction with collagen plays
an important role.
The ICR team explored the role of signals triggered by collagen
in human embryonic kidney cells, a type of cell often used in
studies of this type. They analysed the role of a molecule called
DDR2, which relays signals from collagen as a means of maintaining
tissue structure and function, and is mutated in some forms of
squamous cell lung cancer.
They treated cells with collagen, and found that DDR2 responded
by activating a second protein called SHP-2, in a process that
appears to be important in protecting against the growth of some
cancers. But a specific mutant form of DDR2 present in some squamous
cell lung cancers seemed unable to signal through SHP-2, suggesting
the loss of function had left the tissue vulnerable to cancer
That finding offers an exciting opportunity to design the first
targeted treatments for squamous cell lung cancer, perhaps by
mimicking the action of SHP-2 to re-erect the normal controls
against cancer’s growth in the presence of collagen.
Dr Paul Huang, Team Leader in Protein Networks at The Institute
of Cancer Research, said: “We knew collagen was capable of slowing
the growth of some cancer types, presumably by maintaining the
structure of tissues, but our new study for the first time
identifies how this effect occurs in lung cancer.
“We sifted through data on 428 different proteins stimulated by
collagen, and isolated just one we think can play a key role in
protecting tissues from cancer. Identifying this molecular trigger
opens up the prospect of targeted treatments for squamous cell lung
“Importantly, we also highlighted the duplicitous nature of this
important signalling network. Although we know it directs a lot of
cellular processes that can contribute to cancer — such as
differentiation, proliferation and motility — in the presence of
collagen, it actually seems to protect against cancer. That means we
will need to treat cancers that develop in collagen-rich
environments differently to blood cancers such as leukaemia.”
Professor Alan Ashworth, Chief Executive of The Institute of
Cancer Research, said: “Survival rates for lung cancer remain
extremely poor, and one of the ways to improve this is to discover
new ways of targeting the disease with drugs. This new study is
valuable for two reasons – it identifies an exciting new potential
route for treating lung cancers, and it also shows us why some other
approaches are unlikely to work.
“Scientifically, these results are very interesting as they
demonstrate how one of the most common proteins in the human body
plays a role not only in building the structure of tissues but also
The study was funded by The Institute of Cancer Research (ICR),
the Wellcome Trust and the Biotechnology and Biological Sciences
Research Council (BBSRC).