Cooperative Cancer Groupies

Few words carry more impact than the gentle syllables of cancer. Transform it into any language, its effect is unchanged: cancer, cancro, Krebs, рак … Always that inner tightening as we prepare ourselves for something we’d prefer not to hear. And yet, and yet … like so much of life there is an obverse – more than one in fact. Down the years few things have revealed more of the greatness of the human spirit – the fortitude, resilience and compassion of which mankind is capable. And it’s also a wonderful thing because, whatever its downsides, without cancer we would know far less about the amazing flexibility and adaptability of nature. Endless beautiful examples have been teased from its mysteries by inquisitive, curious and sometimes plain lucky scientific detectives.

Of late a particularly fertile facet has been what one might call the supporting cast: not tumour cells themselves but families that have moved in next door. If the idea that both normal and abnormal may play a role seems a bit strange, recall that, as well as being wonderful, cancer’s also funny – peculiar, that is – in being generated within ourselves: something goes wrong with cells that are perfectly normal and the result is something unusual. A new growth. A neoplasm. And our body reacts as it almost always does when something odd happens: it sends reporters along to find out what’s happening and put a stop to it. These roving sleuths are cells of the immune system – collectively white cells.

As with almost any unusual event – a new kid in school, a spotted celeb, a traffic accident – a crowd has started to gather round. In the body it’s called inflammation and it’s the first sign that our immune response is being switched on. The cellular groupies that turn up at the earliest signs of a tumour are a motley lot: all the broadsheets and tabloids are there, so to speak. But they differ from human onlookers in that each has a job to do. The first response is that some of the groupies release chemical signals that can target tumour cells for destruction by other groupies. The tumour is seen as ‘foreign’, just like an infection, and the response is ‘get rid of it’. We have no idea how efficient this kind of tumour elimination is but we might guess it’s not bad as most cancers don’t appear until we’ve been around for over 60 years.

When a tumour does manage to grow to a detectable size, that protection has clearly been overcome. But astonishingly, when this happens it’s not merely that the anti-tumour armoury has failed. It’s worse than not having enough fire-power: it’s actually been subverted, perverted if you wish, ‘turned’ as John le Carré might say, so that the immune cells that set out as assassins have become genuine groupies. Now the chemical signals they throw onto the tumour stage support growth and protect the cancer cells from destruction. Normal cells, recruited to the scene of cellular abnormality, have become in effect part of the tumour, essential for its survival and continued growth.

A stunning example of the tumour cooperative happens in chronic lymphocytic leukaemia. The leukaemia cells are a typical tumour in that their metabolism is abnormal. One upshot of this is that they make a lot of very reactive things called free radicals that are toxic – that is, will kill the leukemia cells unless they can make a neutralizing chemical called A. But to make A they need a building block B. B needs a carrier to get across the outer membrane into cells and the leukemia cells don’t make that carrier. But one of the ‘groupies’ does: it takes up lots of B, turns it into C and then pumps that out so that the tumour cells are bathed in C – which they can take up. The leukemia cells convert C into B, then make A, which knocks out their free radicals – so they survive and the tumour grows. If you can describe a thriving tumour as wonderful, it’s jaw-droppingly clever. And it’s not all bad news because blocking the transfer of C offers a new drug target for treating the most common adult leukemia in the Western world.

Reference

Zhang, W. et al., (2012). Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nature Cell Biology 14, 276-286.

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3 comments on “Cooperative Cancer Groupies

  1. Pingback: Scattering the Bad Seed | Betrayed by Nature: The War on Cancer

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  3. Pingback: Self Help – Part 1 | Betrayed by Nature: The War on Cancer

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