title: Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.
abstract: Malignant pleural mesothelioma (MPM) is an almost invariably fatal, asbestos-related malignancy arising from the mesothelial membrane lining the thoracic cavities. Despite some improvements in treatment, therapy is not considered curative and median survival following diagnosis is less than 1 year. Although still classed as a rare cancer, the incidence of MPM is increasing, and the limited progress in treating the disease makes the identification of new therapies a priority. As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. In mesothelial cells (MC) and 7 MPM cell lines, growth inhibition by cilengitide was associated with the expression level of its target integrins. Furthermore, cilengitide caused cell detachment and subsequent death of anoikis-sensitive cells. It also suppressed invasion of MPM cells in monolayer and three-dimensional cultures. Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.
authors.affiliation: Asbestos Diseases Research Institute, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Ngan Ching
authors.initials: NC
authors.lastname: Cheng
authors.affiliation: Asbestos Diseases Research Institute, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.affiliation: Asbestos Diseases Research Institute, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Glen
authors.initials: G
authors.lastname: Reid
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008654:Mesothelioma / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010997:Pleural Neoplasms / Q000473:pathology*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D012910:Snake Venoms / Q000494:pharmacology*
chemical_list: D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; D012910:Snake Venoms; C064660:integrin alphaVbeta5; C422910:Cilengitide