| Abstract: |
To investigate the role of integrin signaling and the role of vascular endothelial growth factor (VEGF)-induced microvessel hyperpermeability in tumor cell adhesion in intact microvessels, we used video microscopy to measure the adhesion rates of normal mouse mammary epithelial cells (Nmumg), mouse wild type (WT) and β4 integrin signaling defective mammary tumor cells (1355T) in the post-capillary venules of rat mesentery in vivo. Individual post-capillary venule was perfused with cells (2-4 million/ml) at a rate of ∼1000 μm/s 1) under conditions of normal and increased vessel permeability by 1 nM VEGF, and 2) after pretreatment of cells with antibody blocking α6 integrin. Our results showed that a) 1355? cells adhered 2.2-fold as much as the WT tumor cells under the normal permeability condition in ∼60 mins. This indicates that β4 signaling has differential roles in tumor cell adhesion and in its progression; b) 1nM VEGF increased WT and 1355T cells adhesion by 1.9 folds and 1.4 folds in ∼60 mins, respectively; c) Pretreatment with anti-α6 antibody decreased the WT cell adhesion by 33%, 1355T cell adhesion by 55% under normal permeability condition, and by 36% and 47% under increased permeability by 1 nM VEGF in ∼60 mins; d) the increased permeability by VEGF and blocking α6 integrin have no visible effects on the normal cell adhesion. © 2007 IEEE. |
