P-226THE ROLE OF ENDOTHELIAL CELL ACTIVATION AND VON WILLEBRAND FACTOR IN TUMOUR-ASSOCIATED HYPERCOAGULATION AND METASTASIS FORMATION OF LUNG CARCINOMA

Objectives: Cancer patients hold a high risk for venous thromboembolism associated with poor prognosis due to an enhanced incidence of metastasis. For extravasation and formation of new metastatic foci, circulating tumour cells needs to interact with the vascular endothelium. How this interaction promotes cancer-driven hypercoagulation and metastasis remains unclear. Our previous studies demonstrate that tumour cells release VEGF-A followed by activation of endothelium,release of inflammatory cytokines and the procoagulatory protein von Willebrand factor (VWF) switching the vessel wall into a pro-inflammatory and pro-coagulatory surface. VWF forms intraluminal fibres mediating platelet binding and aggregation. We postulate that VWF fibres in tumour vessels promote tumour-associated coagulation and metastasis. Methods: Fifty-three patients with biopsy-proven lung cancer and 15 healthy controls were included in this study under written consent. The local ethic committee approved the study. Endothelial cell activation was examined locally in tissue sections with high resolution fluorescence microscopy and systemically by determination of the levels of VEGF-A and Ang-2 in citrated serum samples. Systemic levels of VWF antigen were quantified and the activity of the VWF degrading enzyme ADAMTS13 was measured. Results: Evaluation of tumour tissue using immunofluorescence demonstrated pronounced VWF fibre formation and platelet aggregation in tumour vasculature. Analysis of blood samples of lung cancer patients showed significantly increased levels of VWF in tumour patients compared to healthy control. The markers for endothelial cell activation Ang-2 and VEGF-A were clearly increased in tumour patients. A non-significant decrease in enzymatic activity of ADAMTS13 was found. Conclusions: Our support the hypothesis that the tumour microenvironment stimulates the endothelial activation and release of VWF in lung cancer. Our findings provides evidence for a mechanism wherein locally inhibited ADAMTS13 activity promotes VWF fibre formation, mediating platelet binding and occlusion of tumour vessels. In conclusion, further studies are needed to explain the biological role of VWF in tumour progression. Disclosure: No significant relationships.