Von Willebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect

The aim of this study was to explore whether von Willebrand's factor (vWF) plays a role in the adhesion of human colon tumor cells to human endothelia l cells in our coculture system. Cell colony density was evaluated basally (endothelial plus colon tumor cel ls) and following the addition of: purified vWF, vWF plus vWF-blocking anti bodies, antibodies against various integrins and adhesion molecules (alpha (2) b integrin, beta (1) integrin, beta (3), integrin, intercellular adhesi on molecule-1, intercellular adhesion molecule-II, vitronectin receptor CD6 1 CD51, laminin alpha6/beta4 receptor), and various drugs inhibiting the he mostatic system (ticlopidine, heparin, acetyl salicylic acid [ASA], defibro tide, indobuphen, dipyridamole, sulfinpyrazone), Furthermore, VWF concentra tion was measured in the supernatant fluid of the coculture system basally and following the addition of the above-listed drugs, Cell colony density ( as measured by light absorption) increased by 33% following the addition of VWF and returned to a value similar to the basal level with antibodies aga inst vWF, while it did not change significantly following the addition of a ntibodies against the other integrins or adhesion molecules tested. The sam e parameter was reduced by 35% following the addition of ticlopidine, while it showed a smaller or no change with the other drugs tested. Similarly, v WF concentration in the cell coculture supernatant showed the greatest redu ction (from 0.22 to 0.11 mg/mL) following the addition of ticlopidine. Thes e data suggest that vWF mediates the adherence of human tumor cells to huma n endothelial cells and that ticlopidine interferes with this effect. (C) 2 000 Editions scientifiques et medicales Elsevier SAS.