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


OBJECTIVE
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.


CONCLUSIONS
These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.
Terraube
V
V
INSERM U143, Le Kremlin-Bicêtre, France.
Pendu
R
R
Baruch
D
D
Gebbink
M F B G
MF
Meyer
D
D
Lenting
P J
PJ
Denis
C V
CV
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D039302:Integrin alphaVbeta3 / Q000187:drug effects; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D014841:von Willebrand Factor / Q000235:genetics* / Q000494:pharmacology
D039302:Integrin alphaVbeta3; D011994:Recombinant Proteins; D014841:von Willebrand Factor