Work

E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion

Year: 2011

Type: article

Abstract: BACKGROUND: E7080 is an orally active multi-targeted kinase inhibitor whose targets include vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptor (FGFR) and platelet derived growth factor receptors (PDGFR). It has been shown to inhibit tumor angiogenesis by targeting endothelial cells. A number of the targets of E7080 are also expressed on tumor cells and here we have looked at the direct effects of E7080 on tumor cell behavior. METHODS: 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. RESULTS: 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-β 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. CONCLUSION: 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.

Source: BMC Cancer

DOI: 10.1186/1471-2407-11-309

Authors: Hilary Glen, Susan Mason, Hitesh Patel, Kenneth Macleod, Valerie G Brunton

Institutions: Edinburgh Cancer Research, Cancer Research UK Scotland Institute, University of Edinburgh

Language: English

Topic: Fibroblast Growth Factor Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,390