Being told that your breast cancer has spread can be devastating news, and it might seem to come out of the blue. But the secondary tumours that develop, far from appearing out of nowhere, are really at the end of a long journey, one that we’re now beginning to understand in more detail. 

Friday 16 September 2016      Research blog
Professor Clare Isacke and the molecular biology team Breast Cancer Now

Prof Clare Isacke and the molecular biology team at the Breast Cancer Now Tony Robins Research Centre

Before a breast cancer cell can multiply to form a secondary tumour, before it even arrives at its new location, it has to leave the primary breast tumour. One route available to cancer cells is through the blood stream, which they enter by squeezing through the blood vessel wall.

Research announced today, part-funded by Breast Cancer Now, has shed some light on how breast cancer cells are able to do this – and reveal how we might be able to stop this first step on their journey.

Sneaking through walls

Prof Clare Isacke and her team at the Breast Cancer Now Toby Robins Research Centre are interested in how non-cancer cells are involved in the growth and spread of breast cancer. Working in partnership with colleagues based at the University of Heidelberg in Germany, Prof Isacke has turned her attention to a group of non-cancer cells called pericytes. Pericytes are funny-looking things, resembling a spider or an octopus with many long spindly legs which wrap around the smallest of blood vessels – and part of their job is to support and protect the cells that make up the blood vessel walls.

Pericytes on a blood vessel

Pericytes on a blood vessel

Prof Isacke’s interest in pericytes started with studying mice that were genetically-engineered so that they were unable to produce a molecule called ‘endosialin’. Comparing these mice to normal mice, she found that breast tumours grew to about the same size, but that the spread of breast cancer was much reduced in the mice that lacked endosialin. This suggested that endosialin was helping the spread of breast cancer in some way.

One more clue was that these mice that lacked endosialin also had fewer cancer cells in their blood stream, which suggested endosialin was involved in how cancer cells pass through the blood vessel wall. Knowing that endosialin is produced on the surface of pericytes associated with the blood vessels that supply tumours, Prof Isacke and colleagues investigated further.

Ultimately, with many detailed experiments using cells grown in the lab that aimed to replicate the blood vessel wall, the team found that breast tumour cells come into direct contact with pericytes that produce endosialin, which then help the cancer cells get through the blood vessel wall and into the blood.

Breast cancer cells entering blood vessels with the help of pericytes producing endosialin Breast cancer cells entering blood vessels with the help of pericytes producing endosialin (not to scale)

Putting up barriers

The next stage in the research for Prof Isacke and colleagues is to understand precisely how pericytes are helping breast cancer cells enter the blood stream, and exactly how endosialin is involved in this process. It will also be important to understanding how pericytes come to produce endosialin in the first place, and how we might stop the ‘bad’ pericytes without hurting the normal ‘good’ perictyes our blood vessels depend upon.

Fortunately, endosialin is a promising target for drugs, because it is mostly produced only during the development of embryos, and then mainly only reappears during cancer – this means that any drugs that block endosialin might not have such a huge impact on normal healthy cells in the body, and so the risk of severe side-effects could be lower.

Drugs that block endosialin are already in development, and one such drug, called ‘MORAb-004’, is in the very early stages of being tested with cancer patients. It’s too soon to tell – from either Prof Isacke’s research or these early clinical trials – whether blocking endosialin could be an effective treatment breast cancer, but we really look forward to seeing what happens next in this area.

Breaking the link

Today’s research reminds us yet again of how breast cancers do not exist in isolation – they deliberately recruit and exploit non-cancer cells around them. We highlighted some of Prof Isacke’s recent work before, looking at how breast tumours ‘radicalise’ cells called fibroblasts to help them grow.

Stopping tumours from growing and spreading will depend on us being able to break the link between tumours and their environment. Only then will we be stop breast cancer cells from making their first step on their journey that cuts so many lives short.

Breast Cancer Now thanks Walk the Walk and Future Dreams for their generous support towards Professor Clare Isacke’s research.

Watch our video with Professor Clare Isacke about what a day in the lab is like

About the author

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Dr Richard Berks is Senior Research Communications Officer at Breast Cancer Now.

He has a PhD in leukaemia research and a love of statistics.

The Research Communications team keeps our supporters and the public up to date with the exciting progress our scientists are making against breast cancer, as well as research news from around the world.