08 July 2022

High levels of blood-clotting proteins can result in poor outcomes for breast cancer patients, according to an Irish study.

New research from RCSI University of Medicine and Health Sciences, Dublin, found that patients with breast cancer had very high levels of von Willebrand Factor in their blood and that individuals with the highest levels had the poorest outcomes.

Writing in the Journal of Thrombosis and Haemostasis, they say analysing von Willebrand Factor levels may be useful to help predict clinical outcomes in patients with breast cancer.

When they also examined in lab experiments how breast cancer triggers high levels of von Willebrand Factor, they found breast tumour cells cause the release of the clotting protein from endothelial cells, the cells which form the inside lining of blood vessels. This could be helping the breast tumour cells to circulate in the blood stream and may help the breast tumour spread to other organs.

Anticoagulant medication (low-molecular weight heparin) could inhibit this effect by reducing levels of von Willebrand Factor and also preventing the migration of cancer cells across an endothelial cell layer in the lab.

Dr Jamie O’Sullivan, of the Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI, said: “Our findings now show, for the first time, that this blood clotting may be caused by increased levels of a key pro-clotting protein, von Willebrand Factor, and that the breast tumour cells directly interact with the blood vessel wall to promote release of this protein.

“Interestingly, this not only increases risk of blood clotting for these patients, but may also promote breast cancer cells spreading throughout the body via the circulation.

 “Our work helps to better understand why patients with breast cancer have increased risk of blood clots and also why this may contribute to worse disease, cancer progression and spread throughout the body which will have a huge impact on the treatment of breast cancer and the outcomes for patients worldwide.”

Source:

Dhami SPS, Patmore S, Comerford C, Byrne CM, Cavanagh B, Castle J, Kirwan CC, Kenny M, Schoen I, O'Donnell JS, O'Sullivan JM.  (2022) “Breast cancer cells mediate endothelial cell activation, promoting von Willebrand Factor release, tumour adhesion and transendothelial migration.” Journal of Thrombosis and Haemostasis, doi: 10.1111/jth.15794

Link: https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.15794

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