Blocking a single molecule, the amino acid asparagine, can prevent breast cancer spread in mice, according to a new study.
Asparagine is one of the building blocks used to make proteins, and it can be made by the body or taken in from the diet. The study, published in Nature, found that limiting asparagine by different methods can dramatically reduce metastasis of cancerous cells in triple-negative breast cancer mice.
The scientists restricted asparagine availability using three separate strategies. They targeted asparagine synthase, the enzyme that makes asparagine in the body, used a chemotherapy drug called L-asparagine and minimised dietary asparagine intake in mice. All three ways, although they did not affect or improve the primary breast cancer, greatly reduced the ability of these tumours to spread.
'Our work has pinpointed one of the key mechanisms that promotes the ability of breast cancer cells to spread,' said Professor Greg Hannon at the Cancer Research UK Cambridge Institute, and lead study author. 'When the availability of asparagine was reduced, we saw little impact on the primary tumour in the breast, but tumour cells had reduced capacity for metastases in other parts of the body.'
Triple-negative cancers, due to the lack of oestrogen and progesterone hormonal receptors in the cancerous cells, are very resistant to current treatments which have been developed to target these mechanisms. The outcome is more than often metastasis to multiple organs and a high mortality rate.
The implications of this work in mice led the researchers to look at triple-negative cancer data from humans, and they found that where the breast cancer cells showed higher levels of asparagine there were higher rates of metastasis. Interestingly, the spread of other primary cancers agrees with this pattern.
'This finding adds vital information to our understanding of how we can stop cancer spreading – the main reason patients die from their disease,' said Professor Hannon.
Because asparagine can also be obtained from foods, reduced dietary intake in some patients might improve the disease outcome and limit its spread, suggest researchers. Foods rich in asparagine include certain meats, fish, asparagus, soy and legumes among others.
'Our study adds to a growing body of evidence that suggests diet can influence the course of the disease,' said Dr Simon Knott at Cedars-Sinai Centre for Bioinformatics and Functional Genomics, and co-first author of the study.
Professor Hannon added: 'In the future, restricting this amino acid through a controlled diet plan or by other means could be an additional part of treatment for some patients with breast and other cancers.' He cautioned: 'But of course, until human studies are done, this isn't a DIY method to prevent cancer.'
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