In Monday’s Joint ISTH-WFH State-of-the-Art Session, “Novel Functions of VWF”, Stefan Schneider, M.D. discussed the role of von Willebrand Factor (VWF) in coagulation and its link to cancer.
- VWF has long been understood to play a role in coagulation and clot formation, however new roles of VWF in cancer are now being identified.
- The greatest change in our understanding of VWF is the identification of its release from intact endothelial cancer cells, meaning cellular damage is not required to initiate VWF release into the lumen, initiating coagulation and inflammatory responses.
Our understanding of the link between coagulation and cancer continues to expand. This link manifests as an increased risk of venous thromboembolism (VTE) in patients with cancer, but also the contribution of the hemostatic system to cancer metastases. This session, led by Stefan Schneider, M.D., discussed newly elucidated roles for VWF in cancer-associated thrombosis, and more importantly, in the growth and spread of cancer cells.
VWF is one of the most important proteins for platelet adhesion. However, VWF has additional roles, which may be critical to thrombosis in the setting of cancer. VWF is constitutively secreted to the basal side of the endothelial cell to the sub-endothelium and into the lumen of the blood vessel; it is also released following endothelial cell damage. Released VWF can attach in long fibers to an intact cell surface. In this scenario, this procoagulant protein has access to blood flow and can activate hemostatic mechanisms without cellular injury.
This mechanism has been seen in vivo in both basal cell carcinoma cells and melanoma cells, showing that VWF is secreted into the lumen of the blood vessels that are present in these tumors. When analyzing tumors individually, high levels of VWF released directly into the lumen can be measured.
Schneider next sought to determine if blood vessels distant from the tumor were affected by VWF. In a mouse model of melanoma, spontaneous melanoma metastases were seen. In this model, endothelial cells were activated and VWF was released. In mice injected with low molecular weight heparin (LMWH), the anticoagulated mice remained healthy while control mice showed signs of tumor spread.
Tumor cells have high thrombophilic activity. Tumor endothelial cells may be activated by vascular endothelial growth factor or other factors leading to VWF release, platelet adhesion, and leukocyte activation. This may support tumor migration and metastases.