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

J Thromb Haemost. 2006 Mar;4(3):519-26. doi: 10.1111/j.1538-7836.2005.01770.x. Epub 2005 Dec 23.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Integrin alphaVbeta3 / drug effects
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Neoplasm Transplantation
  • Recombinant Proteins / pharmacology
  • von Willebrand Factor / genetics*
  • von Willebrand Factor / pharmacology

Substances

  • Integrin alphaVbeta3
  • Recombinant Proteins
  • von Willebrand Factor