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

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• 作者：Gerald W. Prager ; Eva-Maria Lackner ; Maria-Theresa Krauth ; Matthias Unseld ; Marina Poettler ; Sylvia Laffer ; Sabine Cerny-Reiterer ; Wolfgang Lamm ; Gabriela V. Kornek ; Bernd R. Binder ; Christoph C. Ziel
• 关键词：Cancer ; VEGF ; mTOR protein ; Rapamycin ; Bevacizumab
• 刊名：Molecular Oncology
• 出版年：2010
• 出版时间：April 2010
• 年：2010
• 卷：4
• 期：2
• 页码：150-160
• 全文大小：1423 K

文摘

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.