Open AccessTargeting of VEGF‐dependent transendothelial migration of cancer cells by bevacizumab
Author(s) -
Prager Gerald W.,
Lackner Eva-Maria,
Krauth Maria-Theresa,
Unseld Matthias,
Poettler Marina,
Laffer Sylvia,
Cerny-Reiterer Sabine,
Lamm Wolfgang,
Kornek Gabriela V.,
Binder Bernd R.,
Zielinski Christoph C.,
Valent Peter
Publication year - 2010
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2010.01.002
Subject(s) - bevacizumab , pi3k/akt/mtor pathway , cancer research , vascular endothelial growth factor , mediator , vascular permeability , cancer cell , medicine , secretion , cancer , biology , vegf receptors , pathology , microbiology and biotechnology , signal transduction , chemotherapy
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 VEGF165 as a mediator of effusion formation. VEGF165 was constantly secreted by all cultured tumor cells in an mTOR‐dependent manner, as it was inhibited by the mTOR inhibitor rapamycin. Secreted VEGF165 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.