Collagen clue reveals new drug target for untreatable form of lung cancer

Collagen, the stuff of ligaments and skin, and the most abundant protein in the human body, has an extraordinary role in triggering chemical signals that help protect the body from cancer, a new study reveals.

Scientists at The Institute of Cancer Research, London, have uncovered a series of chemical signals sent out by collagen that appear to protect against cancer's growth.

Boosting those 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 currently exist.

And the findings 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 study was funded by The Institute of Cancer Research (ICR), the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC).

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.

Lung cancer is the second most common cancer in the UK (2010), accounting for 13% of all new cases. It is the second most common cancer in both males (13% of the male total) and females (12%).

In 2010, there were 42,026 new cases of lung cancer in the UK: 23,175 (55%) in men and 18,851 (45%) in women, giving a male:female ratio of more than 12:10. The crude incidence rate shows that there are 76 new lung cancer cases for every 100,000 males in the UK, and 60 for every 100,000 females.

The European age-standardised incidence rates (AS rates) are significantly higher in Scotland compared with the other constituent countries of the UK, and significantly lower in England.

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 growth.

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.