Sowing the Seeds of Cancer

11 January 2009

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Nine out of ten cancer deaths are due to tumours spreading from the original site, the primary tumour, to form secondary tumours in places like the lungs, liver or brain.  Scientists call this metastasis.  Now new research from scientists in the US, UK and Canada has revealed an important molecule called LOX is involved in metastasis, which could lead to new treatments for cancer.

Secondary tumor deposits in the liver from a primary cancer of the pancreasTo explain why LOX is important, we need to go back a bit.  Secondary tumours don't just spring up anywhere.  In the same way that the ground needs to be right for a seed to grow, cancer cells need the right conditions.  Back in 2005, scientists found that special cells move from the bone marrow into organs like the lungs, forming little bundles called pre-metastatic niches.  And it's in these niches that spreading cancer cells grow.

Now Janine Erler and her colleagues have found that a protein called LOX, or lysyl oxidase, plays an important role in forming these niches.  LOX acts a bit like a craftsman, gluing together proteins that form the extracellular matrix - the jelly-like stuff that surrounds our cells.  The researchers think that LOX glues together certain proteins, forming the right kind of environment to attract bone marrow cells, and therefore the right kind of environment for cancer cells to spread into.

Firstly, the team transplanted mice with normal breast cancer cells, or breast cancer cells that had been genetically manipulated so that they didn't contain any LOX.  The scientists found that the mice carrying cancer cells without LOX had far fewer secondary tumours than those with the unchanged cancer cells.  And the LOX-free cancer cells also failed to recruit bone marrow cells.

It seems LOX might also be important in human cancer cells. The scientists took 95 samples of secondary tumours taken from cancer patients, including people with breast, bowel, stomach and oesophageal cancers. And in more than half of the samples, there were high levels of LOX, and clusters of bone marrow cells.

So now that we know LOX is important for this process, scientists can start searching for drugs that might block its actions, which could potentially be used to treat cancer - or even stop it from spreading at all - in the future.

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