Study demonstrates mechanism behind hijacking of TNF controlled response to tumours

Cancer Research UKJun 16 2010

Cancers hijack body's defences to grow and spread

Cancer Research UK scientists have discovered how two genes can 'hijack' control of part of the body's defences against cancer, helping them grow and spread. Their research is published in Developmental Cell1 today (Tuesday).

Part of the body's defence system is controlled by a gene called Tumour Necrosis Factor (TNF) that can stop cancers from developing by killing them. But this same response has also been shown to help promote the growth of cancers.

For the first time, scientists at the Cancer Research UK Beatson Institute in Glasgow have shown how TNF turns to the 'dark side', helping some cancers to grow and move to new parts of the body. They found that the TNF response is hijacked by two genes linked to cancer.

The two genes are a tumour suppressor gene, that promotes tumour growth when deleted, and a tumour promoter gene that can turn cells cancerous when activated.

In their study, using fruit flies (Drosophila melanogaster), they found that cells which lack a tumour suppressor gene and turn cancerous are targeted and killed by the TNF controlled response. But, if the tumour promoter is also activated, cancer cells are not only able to escape the TNF's death signal but also produce a signal to help them spread and grow.

The researchers also showed that all three genes need to be involved for the cancer to fully escape control by the body's defences. If the response is not co-ordinated by TNF, a tumour will develop, but it is a so called benign tumour - unable to spread to other parts of the body.

Dr Marcos Vidal, lead author from Cancer Research UK's Beatson Institute, said: "This is the first time that the mechanism behind this hijacking of the TNF controlled response to tumours has been demonstrated. The next step is to test if these same interactions are taking place in humans. If it is, we could determine which patients will benefit from drugs that stimulate an inflammatory response and those who would benefit from drugs that dull these signals down, preventing the cancer from using the TNF to spread and grow."

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "Cancers are a complex interplay and competition between the body's defences and the cancer's attempts to grow and spread. This research reveals more about these interactions and could one day open up new approaches for treating cancer."