Von Willebrand Factor and Cancer; metastasis and coagulopathies.

2020 
Von Willebrand factor (VWF) is a multimeric procoagulant plasma glycoprotein that mediates platelet adhesion along the endothelium. In addition to its role maintaining normal haemostasis, more recently novel biological functions for VWF have been described, including inflammation, angiogenesis and metastasis. Significantly increased plasma VWF levels have been reported across a variety of cancer patient cohorts. Given that VWF is established as a risk factor for venous thrombosis, this is of direct clinical importance. Moreover, elevated VWF has also been observed localized within the tumour microenvironment, correlating with advanced disease stage and poorer clinical outcome. Critically, evidence suggests that elevated VWF levels in cancer patients may not only contribute to cancer associated coagulopathies but may also mediate cancer progression and metastasis. Studies have shown that VWF can promote pro-inflammatory signalling, regulate angiogenesis and vascular permeability which may facilitate tumour cell growth and extravasation across the vessel wall. Endothelial secreted VWF multimers contribute to the adhesion and transendothelial migration of tumour cells key for tumour dissemination. In support of this, VWF inhibition attenuated metastasis in vivo. Perhaps most intriguingly, specific tumour cells have been reported to acquire de novo VWF expression which increases tumour-platelet heteroaggregates and confers enhanced metastatic activity. Current knowledge on the roles of VWF in cancer and in particular its contribution to metastasis and cancer associated coagulopathies is summarised in this review.
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