%0 Journal Article
%T E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion
%A Hilary Glen
%A Susan Mason
%A Hitesh Patel
%A Kenneth Macleod
%A Valerie G Brunton
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-309
%X Using a panel of human tumor cell lines we determined the effect of E7080 on cell proliferation, migration and invasion. Inhibition of FGFR and PDGFR signaling in the cells was measured.E7080 had little effect on tumor cell proliferation. However, it blocked migration and invasion at concentrations that inhibited FGFR and PDGFR signaling. Knock-down of PDGFR-¦Â in U2OS osteosarcoma cells also inhibited cell migration which, could not be further inhibited in the presence of E7080. Furthermore, E7080 could not inhibit the migration of a PDGFR negative cell line.E7080 does not significantly affect tumor cell proliferation but can inhibit their migration and invasion at concentrations that both inhibit its known targets and are achievable clinically.Angiogenesis, the formation of new blood vessels, is required for tumor growth and metastasis [1,2]. The ability of tumors to promote angiogenesis is driven by expression of pro-angiogenic factors such as VEGF, bFGF, PDGF and transforming growth factor-¦Â (TGF-¦Â) of which VEGF is the most important [1,3]. VEGF exerts its actions through two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, but it is signaling via VEGFR-2 that is important for tumor angiogenesis [4]. A third VEGF receptor VEGFR-3, is important for lymphangiogenesis and is activated by two different ligands, VEGF-C and VEGF-D [5]. In view of the dependence of tumors on angiogenesis for sustained growth, targeting angiogenesis has been the focus of much research into new anti-cancer therapies in recent years [6]. Direct angiogenesis inhibitors target endothelial cells by inhibiting their ability to proliferate, migrate and form new blood vessels. The first example of this was the use of an antibody to VEGF, which was able to inhibit the growth of tumors in mouse models [7]. Subsequently a humanized version of this antibody, bevacizumab, was developed which showed promising evidence of efficacy in pre-clinical models. However, this was not translated into the clinic
%U http://www.biomedcentral.com/1471-2407/11/309