Breakthrough Breast Cancer-funded scientists have discovered a gene that prevents the spread of breast cancer by stopping tumour cells from becoming ‘sticky’.
The study, conducted by Breakthrough-funded researchers at The Institute of Cancer Research, London, and published in the journal Cancer Discovery, found that breast cancer cells with lower activity in the gene become ‘sticky’, allowing them to spread and colonise new sites in the body.
The gene, ST6GalNAc2, seems to prevent cancer cells from attaching molecules of a protein called galectin-3 – which gives cells their ‘stickiness’ – to their surface. This discovery could open new methods of treatment that prevent breast cancer spread.
Using a powerful technique called RNAi screening, the team switched off more than 1,000 genes in breast cancers grown in mice, and monitored the animals for the development of secondary tumours. By analysing the DNA from secondary tumours that developed in the lungs of the mice, they were able to identify several genes, including ST6GalNAc2, that when switched off contributed to the formation of these tumours.
In reviewing ST6GalNAc2 activity in a large database of breast cancer patients, the researchers found that gene activity was particularly low in a subtype of patients with oestrogen receptor negative (ER-) breast cancer.
The results suggest that giving some women with ER- breast cancer drugs that target galectin-3 – drugs that already exist and are usually well-tolerated – could slow the spread of their cancer.
Study leader Professor Clare Isacke, Professor of Molecular Cell Biology at The Institute of Cancer Research, London, said:
“Being ‘sticky’ is important for cancer cells because it allows them to spread and invade new sites around the body. Our study found that a particular gene, called ST6GalNAc2, seems to play an important role in preventing tumour cells from gaining this stickiness. Some women with breast cancer may be at higher risk of their cancer spreading to new parts of the body because of the silencing of this gene.
“Our study also underlines the vital importance of understanding the process of metastasis in order to find new treatments for cancer.”
Dr Matthew Lam, Research Officer at Breakthrough Breast Cancer, explains how these findings could be applied to patients:
“Almost all deaths from breast cancer are caused by the metastatic, or secondary, form of the disease which equates to 1,000 women dying each month in the UK. By analysing samples from real patient tumours and looking to see if the ST6GalNAc2 gene was switched on or off, the researchers suggest that the ST6GalNAc2 gene could be used as a marker to select patients with a particular type of breast cancer that would benefit from treatment with a drug that prevents galectin-3 from making the tumour cells ‘sticky’. Clinical trials have already shown these drugs to be safe and could provide a new treatment option for the prevention of secondary disease.
“We can’t currently identify which women or men will go on to develop secondary breast cancer. That's why Breakthrough is leading the way to find out more about this fatal form of the disease through our research work. Professor Clare Isacke and her team are at the forefront of this fight and they dedicate their work to finding out how breast cancer spreads and how we can stop that from happening. Once we know the answers to these questions, we will go a long way towards stopping women dying from breast cancer.”