Scientists have discovered that bowel cancercells can transform into skin or muscle cells, allowing them to spread more aggressively. This breakthrough offers hope for treating the increasing rates of the disease, especially among young people.
A study conducted by the Cancer Research UK Scotland Centre and the University of Edinburgh revealed that a critical step in aggressive bowel cancer involves cells losing their original identity, a process known as cellular plasticity. Researchers found that the disease spreads when colonic cells begin to resemble squamous cells, which form skin, or muscle cells.
Bowel cancer is the second most common cause of cancer deaths in the UK. It claims the lives of 16,800 people in Britain, including 1,700 in Scotland, every year and is increasingly being diagnosed in younger people internationally.
A recent study by the American Cancer Society published in The Lancet Oncology showed early-onset bowel cancer rates in adults aged 25-49 are rising in 27 of 50 countries studied, and increasing faster in young women in Scotland and England than in young men.
Scotland is disproportionately affected with around 4,000 people diagnosed each year overall, according to Cancer Research UK.
The latest study found bowel cancer cells can adapt to resemble skin cells, which can tolerate much harsher day-to-day conditions due to their role and position protecting the outside of the body, and also muscle cells, both of which are more “robust”.
Cellular plasticity was found to be an important element in bowel cancer metastasis – when it spreads and becomes harder to treat.
Researchers hope identifying this and preventing it could help make current treatments more effective and stop the disease from spreading.
The study also examined a particular gene called Atrx which was already associated with aggressive forms of bowel cancer.
Using mice and human tissue samples, researchers found the loss of this gene resulted in increased metastatic tumours which spread from the bowel to the liver, lymph nodes and the diaphragm.
Key to the ability of these cells to spread is that they shed their identity of colonic cells and resembled squamous cells which form skin, or cells that resemble muscle.
The paper, “Loss Of Colonic Fidelity Enables Multilineage Plasticity And Metastasis”, is published in Nature. The research received funding from the Medical Research Council and the European Research Council.
Dr Kevin Myant, of the Institute of Genetics and Cancer at the University of Edinburgh and the Cancer Research UK Scotland Centre, said: “With more and more younger people being diagnosed with bowel cancer, it’s vital we understand how this disease grows and develops.
“Our research has discovered one way that aggressive bowel cancer is able to spread is by ‘shapeshifting’ to resemble skin or muscle cells rather than bowel cancer cells.
“This finding will hopefully allow us to develop new treatments to stop these cells changing and prevent the cancer spreading, when it becomes much harder to treat.”
Lead researcher Dr Patrizia Cammareri said: “Skin cells can tolerate much harsher day-to-day conditions than other types of cells – due to their role and position protecting the outside of the body – so this may be a strategy to help the bowel cancer cells become more robust and enable them to spread around the body.
“Metastasis is a leading cause of cancer death and a key focus for cancer research, so this finding could be pivotal in halting the progression of aggressive cancer and providing better outcomes for patients.”
Cancer Research UK director of research, Dr Catherine Elliott, said: “Diagnosing and treating cancer early and preventing spread to other parts of the body offers the best chance of a positive outcome for patients so research like this, which could lead to new ways to stop that spread, offers great hope.
“Bowel cancer is of increasing concern globally, which is why we invested £5.5m to the CRC-STARS initiative (Colorectal Cancer – Stratification of Therapies through Adaptive Responses) jointly led by our Cancer Research UK Scotland Institute, which will bring together more than 40 bowel cancer experts, including researchers who worked on this project, to find new and kinder ways to tackle this disease.”
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