Is the von Willebrand Factor Linked to Metastasis of Breast Cancer?

By: Anna Fanelli
Posted: Wednesday, August 24, 2022

According to a study published in the Journal of Thrombosis and Haemostasis, patients with breast cancer had very high levels of von Willebrand factor (VWF) in their blood, and those with the highest levels tended to have the poorest outcomes. Therefore, Jamie O’Sullivan, PhD, of the Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland (RCSI), Dublin, and colleagues suggest that analysis of VWF levels may be useful to help predict clinical outcomes in patients with breast cancer.

“Our findings now show, for the first time, that this blood clotting may be caused by increased levels of a key proclotting protein, von Willebrand Factor, and that the breast tumor 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,” said Dr. O’Sullivan in a press release from the RCSI University of Medicine and Health Sciences.

The VWF levels were measured by enzyme-linked immunoassay (ELISA). Primary endocannabinoids were used to assess tumor-induced activation, angiogenesis, tumor adhesion, and transendothelial migration.

Patients with metastatic breast cancer have markedly elevated plasma VWF antigen levels, which the investigators believe correlate with poorer survival. MDA-MB-231 and MCF-7 breast cancer cells induce secretion of VWF, angiopoietin-2, and osteoprotegerin from primary endocannabinoids, which is further enhanced by the presence of platelets. Furthermore, vascular endothelial growth factor-A (VEGF-A) seems to play an important role in modulating breast cancer–induced VWF release. Moreover, VEGF-A from breast tumor cells also contributes to a proangiogenic effect on primary endocannabinoids. VWF multimers secreted from primary endocannabinoids, in response to tumor-VEGF-A, mediate adhesion of breast tumor cells along the endothelium. Low–molecular-weight heparin inhibits VWF breast tumor adhesion and transendothelial migration.

According to the study authors, these findings highlight the significant crosstalk between tumor cells and the endothelium, including increased VWF secretion, which in turn may contribute to tumor metastasis.

Disclosure: The research was funded by LEO Pharma through an industry partnership with the Irish Research Council.

Journal of Thrombosis and Haemostasis

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