Effects of VEGF on MDA-MB-435s cancer cell adhesion to microvessel walls in vivo

To investigate whether vascular endothelial growth factor (VEGF) increases cancer cell adhesion to intact microvessels, we measured adhesion rates of MDA-MB-435s human breast cancer cells in the postcapillary venule of rat mesentery by in vivo video microscopy. An individual postcapillary venule in the mesentery was cannulated via a glass micropipette filled with cancer cells and 1% BSA Ringer solution (control) or that with additional 1nM VEGF. The perfusion was done by a water manometer connected to the micropipette and the perfusion velocity was ~1 mm/s. Cell adhesion was measured as the number of adherent cells in a vessel segment for ~ 60 min. Our results showed that during both control and the VEGF treatment, the number of adherent cells increased almost linearly with time over ~ 60 min. The VEGF treatment increased the adhesion rates of MDA-MB-435s by 1.6-fold. We also measured cancer cell adhesion after pretreatment of cells with an antibody blocking VEGF and pretreatment of the microvessel with VEGF receptor (KDR/Flk-1) inhibitor, SU1498. Both anti-VEGF and SU1498 significantly reduced cell adhesion (P<0.05). Our results indicate that VEGF enhances cancer cell adhesion to the normal microvessel wall, and further suggest that VEGF and its receptor, KDR/Flk-1, contribute to mammary cancer cell adhesion to vascular endothelium in vivo.