Targeting of VEGF-dependent transendothelial migration of cancer cells by bevacizumab

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

doi:10.1016/j.molonc.2010.01.002

« Previous Next »Molecular Oncology
Volume 4, Issue 2 , Pages 150-160, April 2010

Targeting of VEGF-dependent transendothelial migration of cancer cells by bevacizumab

Gerald W. Prager
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
- Both the authors contributed equally to this work.
Eva-Maria Lackner
- Department of Ophthalmology, Medical University Graz, A-8020 Vienna, Austria
- Both the authors contributed equally to this work.
Maria-Theresa Krauth
- Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, A-1090 Vienna, Austria
Matthias Unseld
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
- Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria
Marina Poettler
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
Sylvia Laffer
- Ludwig Boltzmann, Cluster Oncology, A-1090 Vienna, Austria
Sabine Cerny-Reiterer
- Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, A-1090 Vienna, Austria
Wolfgang Lamm
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
Gabriela V. Kornek
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
Bernd R. Binder
- Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria
Christoph C. Zielinski
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, A-1090 Vienna, Austria
- Ludwig Boltzmann, Cluster Oncology, A-1090 Vienna, Austria
Peter Valent
- Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, A-1090 Vienna, Austria
- Ludwig Boltzmann, Cluster Oncology, 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.

Received 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.

Keywords: Cancer, VEGF, mTOR protein, Rapamycin, Bevacizumab