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

August 29, 2013

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 '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 , 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 , 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 .

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 cancer.

"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 -rich environments differently to blood cancers such as leukaemia."

Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: "Survival rates for 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 in cancer."

Explore further: Experimental drugs for breast cancer could treat lung cancer too

More information: Squamous cell cancer accounts for around 25 per cent of all lung cancer cases (Heist, R.S., et al., J Thorac Oncol, 2012. 7(5): p. 924-33).

Related Stories

Experimental drugs for breast cancer could treat lung cancer too

August 13, 2013
Cancer Research UK -funded scientists have discovered that experimental drugs first developed for breast and ovarian cancer could be used to treat the most common type of lung cancer, reveals research published in Oncogene ...

Scientists detail critical role of gene in many lung cancer cases

August 29, 2013
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a well-known cancer-causing gene implicated in a number of malignancies plays a far more critical role in non-small cell lung cancer, ...

Changes to cartilage linked to bone cancer offers a possible new diagnostic approach

June 17, 2013
(Medical Xpress)—For the first time, researchers from The Wellcome Trust Sanger Institute, the Royal National Orthopaedic Hospital and UCL Cancer Institute, have linked a gene central to the production of cartilage, COL2A1, ...

Spotting ovarian cancer, before it's too late

December 19, 2012
(Medical Xpress)—At just 28 percent, the five-year survival rate for women diagnosed with ovarian cancer is much lower than in other cancer cases. And, the disease can easily go unnoticed, making it difficult to find effective ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.