title: Targeting of VEGF-dependent transendothelial migration of cancer cells by bevacizumab.
abstract: Cancer progression is often associated with the formation of malignant effusions. Vascular endothelial growth factor (VEGF) is a major regulator of vascular permeability and has been implicated as mediator of tumor progression. We examined the production and secretion of VEGF(165) in various primary cancer cells derived from malignant effusions, and the role of exogenous VEGF(165) as a mediator of effusion formation. VEGF(165) was constantly secreted by all cultured tumor cells in an mTOR-dependent manner, as it was inhibited by the mTOR inhibitor rapamycin. Secreted VEGF(165) showed functional activity by inducing endothelial leakiness and tumor cell-transendothelial migration in vitro, effects which could be reverted by the anti-VEGF antibody bevacizumab. Thus, mTOR inhibitors as well as bevacizumab should be considered as potential agents in cancer patients suffering from malignant effusions.
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Prager
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Lackner
authors.forename: Maria-Theresa
authors.initials: MT
authors.lastname: Krauth
authors.forename: Matthias
authors.initials: M
authors.lastname: Unseld
authors.forename: Marina
authors.initials: M
authors.lastname: Poettler
authors.forename: Sylvia
authors.initials: S
authors.lastname: Laffer
authors.forename: Sabine
authors.initials: S
authors.lastname: Cerny-Reiterer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lamm
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Kornek
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Binder
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004727:Endothelium / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus