Researchers find ‘doorway’ in blood vessels that helps breast cancer cells spread through the body

In collaboration with the Press Association
Three specific types of cells all work together to let cancer cells escape into the blood stream. Image courtesy of Dr Allison Harney.

Using real-time imaging technology, US researchers may have identified how breast cancer cells can escape into the blood stream and spread through the body.

“These findings raise the possibility that blood vessel leakiness, and the entry of cancer cells into the blood may be targeted by cancer therapies.” - Dr Erik Sahai, Cancer Research UK

The team say the work, which was carried out in mice, could lead to new ways to use drugs to prevent cancer from spreading.

Their findings, published in Cancer Discovery, showed that cancer cells near blood vessels can interact with a type of white blood cell called macrophages, causing them to release to a protein known as vascular endothelial growth factor (VEGF). This seems to cause a local increase in blood vessels’ ‘leakiness’ or permeability.

While the effect is temporary, it can last long enough to create a ‘doorway’ for cancer cells to enter the blood stream and spread.

The finding builds on previous work from the team, who are based at both the Albert Einstein Cancer Center, and the Montefiore Einstein Center for Cancer Care in New York.

This had suggested that breast cancer spreads when three specific cells - an endothelial cell (which lines the blood vessels), a macrophage, and a tumour cell that can produce high levels of a protein called Mena - are in direct contact. 

This site is known as a tumour microenvironment of metastasis, or TMEM, and is where blood vessels appear to become permeable and let tumour cells escape. 

“But what regulates that permeability hasn't been clear. Based on our latest imaging studies, we can now say that this phenomenon is regulated by TMEM macrophages," said lead author Allison Harney.

Dr Erik Sahai, a Cancer Research UK expert in cell movement at the Francis Crick Institute said that, while there was more research to do, the findings opened up the possibility of new ways to treat the disease.

“We know that tumour blood vessels can be leaky, but by using cutting-edge imaging techniques this new study shows this propensity to leak can be switched on and off by a particular type of immune cell working together with cancer cells.

“These findings raise the possibility that blood vessel leakiness, and the entry of cancer cells into the blood may be targeted by cancer therapies,” said Dr Sahai, pointing out that the VGEF protein produced by macrophages in the process is already the target of existing cancer drugs, such as sunitinib and bevacuzimab

"But further work will be needed to find out the best ways of using this to help improve treatments,” he added.

References

  •  Harney, Allison. 'Real-Time Imaging Reveals Local, Transient Vascular Permeability, And Tumor Cell Intravasation Stimulated By Tie2hi Macrophage–Derived VEGFA'. Cancer Discovery (2015): DOI: 10.1158/2159-8290.CD-15-0012