Effects of VEGF on adhesion of mammary carcinoma cells to brain microvascular endothelium

Vascular endothelial growth factor (VEGF) has been shown to increase the adhesion of human breast cancer cells to human brain endothelium [1]. However, how VEGF accomplishes this is not well understood. We hypothesize that VEGF compromises the integrity of brain microvascular endothelium is one mechanism to increase the tumor cell adhesion. To test our hypothesis, using a Transwell system, we measured the permeability of a cell monolayer of bEnd3 to FITC-labeled BSA, P^BSA. We observed that P^BSA significantly increased from 4.17 ± 0.67 × 10^-7cm/s to 5.20 ± 0.31 × 10^-7cm/s after 5-60 min treatment with 1 nM VEGF. Correspondingly, after 60 min treatment with 1 nM VEGF, the adherent mouse ErB2-transformed mammary carcinoma cells increased from 38 ± 13/mm² to 67 ± 8/mm² for a wild type; from 40 ± 5/mm² to 56 ± 3/mm² for the ß4 mutant. Pretreatment of the cancer cells with ¿6, ß1, ¿5 integrin antibodies and pretreatment of the cell monolayer with laminin-5 antibody significantly decreased the adhesion of WT and 1355T. Our results suggest that ¿6ß4, ¿6ß1, ¿5ß1 and their ligand, laminin-5, play a role in breast tumor cell adhesion, and that VEGF enhances the adhesion by compromising the integrity of bEnd3 monolayer.