Vascular Endothelial Growth Factor Partially Inhibits the Trastuzumab-Mediated Antibody-Dependent Cellular Cytotoxicity of Human Monocytes

Vol. 72, No. 3-4, 2007

Free Abstract Article (Fulltext) Article (PDF 431 KB)

Laboratory/Clinical Translational Research

Vascular Endothelial Growth Factor Partially Inhibits the Trastuzumab-Mediated Antibody-Dependent Cellular Cytotoxicity of Human Monocytes
Kousaku Mimura, Koji Kono, Akihiro Takahashi, Yoshihiko Kawaguchi, Yoshiki Mizukami, Hideki Fujii

First Department of Surgery, University of Yamanashi, Yamanashi, Japan

Address of Corresponding Author

Oncology 2007;72:172-180 (DOI: 10.1159/000112803)

Key Words

Vascular endothelial growth factor
Monocyte
Antibody-dependent cell-mediated cytotoxicity
Trastuzumab
Flt-1

Abstract

Background: Vascular endothelial growth factor (VEGF) is produced by almost all cancer cells and VEGF receptor 1 (R1) (Flt-1) is abundantly expressed on human monocytes. In the present study, we investigated whether VEGF affects the antibody-dependent cell-mediated cytotoxicity (ADCC) of human monocytes mediated by trastuzumab. Methods: HER-2-expressing tumor cell lines (MKN-7, TE-4 and SKOV-3) were evaluated for trastuzumab-mediated ADCC of human monocytes in the presence of VEGF₁₆₅. The trastuzumab-mediated, monocyte-derived ADCC were treated with the anti-human blocking VEGF R1 or VEGF R2 mAb. VEGF-induced intracellular signaling on monocytes was quantified with ELISA kits. Results: VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab. The VEGF-induced deficiency of human monocytes for ADCC was completely recovered by the anti-human blocking VEGF R1 mAb, while the anti-VEGF R2 blocking mAb did not have any effect. Furthermore, VEGF treatment enhanced the phospho-Erk 1/2 in human monocytes. Conclusion: VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab, and this inhibition was mainly mediated by VEGF R1 (Flt-1).

Author Contacts

Koji Kono, MD, PhD
First Department of Surgery, University of Yamanashi
1110 Shimokato, Chuo City
Yamanashi 409-3898 (Japan)
Tel. +81 55 273 7390, Fax +81 55 273 9574, E-Mail kojikono@yamanashi.ac.jp

Article Information

Received: March 31, 2007
Accepted after revision: July 4, 2007
Published online: December 20, 2007
Number of Print Pages : 9
Number of Figures : 8, Number of Tables : 0, Number of References : 38

Medline Abstract (ID 18097168)

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