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Vascular endothelial growth factor enhances cancer cell adhesion to microvascular endothelium in vivo
Author(s) -
Shen Shang,
Fan Jie,
Cai Bin,
Lv Yonggang,
Zeng Min,
Hao Yanyan,
Giancotti Filippo G.,
Fu Bingmei M.
Publication year - 2010
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2009.050260
Subject(s) - endothelium , in vivo , adhesion , cell adhesion , endothelial stem cell , angiogenesis , cancer , cancer research , microbiology and biotechnology , biology , chemistry , medicine , in vitro , endocrinology , biochemistry , organic chemistry
To investigate whether vascular endothelial growth factor (VEGF) enhances cancer cell adhesion to normal microvessels, we used in vivo video microscopy to measure adhesion rates of MDA‐MB‐435s human breast cancer cells and ErbB2‐transformed mouse mammary carcinomas in the postcapillary venules of rat mesentery. An individual postcapillary venule in the mesentery was injected via a glass micropipette with cancer cells either in a perfusate of mammalian Ringer solution containing 1% bovine serum albumin as a control, or with the addition of 1 n m VEGF for test measurements. Cell adhesion was measured as either the number of adherent cells or the fluorescence intensity of adherent cells in a vessel segment for ∼60 min. Our results showed that during both control and VEGF treatments, the number of adherent cells increased almost linearly with time over 60 min. The VEGF treatment increased the adhesion rates of human tumour cells and mouse carcinomas 1.9‐fold and 1.8‐fold, respectively, over those in control conditions. We also measured cancer cell adhesion after pretreatment of cells with an antibody blocking VEGF or an antibody blocking α6 integrin, and pretreatment of the microvessel with VEGF receptor (KDR/Flk‐1) inhibitor, SU1498, or anti‐integrin extracellular matrix ligand antibody, anti‐laminin‐5. All antibodies and inhibitor significantly reduced adhesion, with anti‐VEGF and SU1498 reducing it the most. 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, as well as integrins of tumour cells and their ligands at the endothelium, contribute to mammary cancer cell adhesion to vascular endothelium in vivo .