New research reveals the role a molecule called Endo180 plays in breast cancer spreading and becoming incurable.

Clare Isacke standing in her lab with her research team

New findings from the Breast Cancer Now Toby Robins Research Centre

Researchers from the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research in London, found that when cells surrounding a tumour can’t make a molecule called Endo180, breast cancer’s ability to grow and spread to other parts of the body is extremely limited.

The next step is to understand whether Endo180 would be a suitable target for new breast cancer treatments.

An approach like this would block breast cancer’s ability to spread and become incurable. It could potentially work for all types of breast cancer as well as other cancers.

Other cells supporting cancer growth

Researchers led by Professor Clare Isacke found that the Endo180 molecule is present in high quantities in tissues surrounding breast tumours. They found that Endo180 was only made by a cell type called cancer-associated fibroblasts, or CAFs. CAFs are found in the tumour and its surroundings and are known to help breast cancer grow and spread to other parts in the body.

Scientists found that, as breast cancer cells grow, they stimulate normal healthy fibroblasts to become CAFs and make more of this molecule. The Endo180 molecule helps create an environment that allows breast cancer to grow.

Breast cancer cells from the main 'types' of the disease – oestrogen receptor positive (ER+), HER2 positive (HER2+) and triple negative – all seemed to be able to do this.

Looking for better ways to treat the disease

Researchers found in mice that without Endo180, breast tumours couldn’t grow as well. Their ability to spread to other parts of the body was also lessened. This led scientists to believe that high levels of Endo180 around the tumour could help the cancer to spread.

They then investigated how breast cancer’s ability to grow and spread is disrupted when Endo180 isn't there, and how tumours might adapt if Endo180 was targeted as part of treatment. In experiments in the lab, they found that breast cancer cells can eventually find a way to overcome the lack of Endo180 in their environment, gaining some functions and abilities that would otherwise be carried out by CAFs.

Next, Professor Isacke and her team will be investigating if targeting the Endo180 molecule with a drug is a suitable new approach to treating breast cancer. Most cancer treatments work by directly killing cancer cells. This new approach would be targeting other cells, like CAFs, that surround the cancer and support its growth. Researchers hope it would stop breast cancer growing and spreading.

Professor Clare Isacke, Professor of Molecular Cell Biology in the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, said:

'The main reason cancer drugs stop working is that tumour cells adapt and evolve, developing mechanisms to avoid being killed by the drug. Coming up with strategies to target the cells that surround and support tumours and identifying drugs that can do this provides another line of attack that could be used against multiple different types of cancer. One advantage to this approach is that CAFs are much less likely to develop mechanisms to avoid the effects of cancer drugs.

'We are now looking at whether Endo180 could be an effective target in treating breast cancer, as this may be a way to prevent CAFs helping cancer cells grow and spread, therefore stripping away one of cancer’s mechanisms for growth, making it more difficult for the tumour cells to thrive.'

The research was published in the journal Nature Communications and has been funded by Breast Cancer Now and Worldwide Cancer Research.

Breast Cancer Now thanks Walk the Walk for their previous support of Professor Isacke’s research.


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