| | Targeting of VEGF-dependent transendothelial migration of cancer cells by bevacizumabReceived 28 August 2009; received in revised form 29 December 2009; accepted 4 January 2010. published online 15 January 2010. 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 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. a Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria b Department of Ophthalmology, Medical University Graz, A-8020 Vienna, Austria c Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, A-1090 Vienna, Austria d Ludwig Boltzmann, Cluster Oncology, A-1090 Vienna, Austria e Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria  Corresponding author. Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, A-1090 Vienna, Austria. Tel.: +43 1 40400 6085; fax: +43 1 40400 4030.
PII: S1574-7891(10)00003-7 doi:10.1016/j.molonc.2010.01.002 © 2010 Federation of European Biochemical Societies. Published by Elsevier Inc. All rights reserved. | |
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