Increased metastatic potential of tumor cells in von Willebrand factor‐deficient mice

• Published in: Journal of thrombosis and haemostasis Vol. 4; no. 3; pp. 519 - 526
• Main Authors: TERRAUBE, V., PENDU, R., BARUCH, D., GEBBINK, M. F. B. G., MEYER, D., LENTING, P. J., DENIS, C. V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Inc 01-03-2006
• Subjects: Animals; Carcinoma, Lewis Lung - pathology; Cell Adhesion - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Dose-Response Relationship, Drug; experimental metastasis; Integrin alphaVbeta3 - drug effects; Lung Neoplasms - pathology; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; melanoma cells; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Neoplasm Transplantation; Recombinant Proteins - pharmacology; von Willebrand Factor - genetics; von Willebrand Factor - pharmacology; von Willebrand factor‐deficient mice
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2005.01770.x

Background: The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet–tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis.Objectives: To investigate whether VWF is involved in metastasis development.Methods: In a first step, we characterized the interaction between murine melanoma cells B16‐BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild‐type and VWF‐null mice following the injection of B16‐BL6 cells or Lewis lung carcinoma cells.Results: In vitro adhesion assays revealed that VWF is able to promote a dose‐dependent adhesion of B16‐BL6 cells via its Arg‐Gly‐Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF‐null mice compared with the wild‐type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis.Conclusion: These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.