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Bonnie and Clyde

IL-25 and its receptor are like a molecular Bonnie and Clyde

Scientists are constantly asking why so many of us get cancer, but perhaps an equally interesting question is why so many of us don’t.

Every single day, the DNA in our cells comes under constant attack – partly from toxins and radiation in our environment, but more regularly from the by-products of chemical reactions that keep us alive.

This means that we generate tumour-prone cells on a daily basis. So how do our bodies prevent these from developing into cancer?


Peering through the net curtains

The answer might lie in a number of phenomena collectively called ‘tumour surveillance’, in which cancerous cells are ruthlessly sought and destroyed.

Regular readers will be familiar with the processes involved; the injured cell switches on its own tumour suppressor proteins (such as p53), which, together with the ‘local environment’ in a tissue, ensure that errant cells either stop dividing or commit suicide. Survivors are left to face the wrath of the immune system where circulating white blood cells target and gobble up those that dare slip through the net.

But this isn’t the whole picture. Reporting in the journal Science Translational Medicine, a research team in the US have revealed a new level of protection; the tumour cell’s healthy counterparts might also play their part in tumour surveillance.

A hidden assassin

The team, led by Professors Mina Bissell and Wen-Hwa Lee, were studying the communication between breast cancer cells and their disease-free neighbours. To their amazement, they noticed that when they tried to grow breast cancer cells in nutrient broth that had previously been used to grow healthy breast cells, the breast cancer cells started to die. So there was a molecular ‘hitman’ lurking in the liquid – a chemical signal that could specifically hunt down cancer cells. But who was he?

To isolate their assassin from the hundreds of others swirling around in the broth, they conducted a series of painstaking experiments that led them to a short-list of six molecules. One molecule, already known for its role in inflammation, also killed breast cancer cells. Its name was interleukin-25 (IL-25), a protein produced by the immune system.

Researchers regularly find molecules that kill cancer cells – indeed, anyone who’s ever worked with cells in a lab knows it’s usually harder to keep them alive. So what makes IL-25 special?

These results are interesting because IL-25 had absolutely no effect whatsoever on healthy cells; it exclusively killed tumour cells. The scientists were intrigued by this observation and wanted to understand what lay at the heart of this preference.

Bonnie and Clyde

It turns out that cancer cells often have a protein called IL-25R (for ‘IL-25 Receptor’) on their surface, which acts as Bonnie to IL-25’s Clyde. Disaster only strikes when IL-25 and IL-25R come together and – here comes the clever bit – healthy cells produce next to no IL-25R. As a result, they remain safe from harm. The researchers are now looking at why and under what circumstances cancer cells start making IL-25R, but suspect that it might in some way fuel their growth.

The team think that during breast cancer development, rogue breast cells distinguish themselves by producing IL-25R.   Meanwhile, their healthy counterparts calmly deal with the problem by producing IL-25 to keep these errant neighbours in check. The scientists believe that this system holds impressive potential, and predict a future in which targeting IL-25R could form the basis of new diagnostic tests and treatments for breast cancer.

This isn’t just idle speculation. Similar studies on a protein called HER2/neu led to the development of the breast cancer drug trastuzumab – better known as Herceptin.    There’s still a lot more work to be done in the lab to turn this discovery into an anti-cancer treatment, but these initial results suggest that it’s well worth investigating further.

Safia Danovi, Senior Science Information Officer

Reference

Furuta, S. et al. (2011). IL-25 Causes Apoptosis of IL-25R-Expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells Science Translational Medicine, 3 (78), 78-78 DOI: 10.1126/scitranslmed.3001374