Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

Vascular endothelial growth factor partially inhibits the trastuzumab-mediated antibody-dependent cellular cytotoxicity of human monocytes.

Mimura K, Kono K, Takahashi A, Kawaguchi Y, Mizukami Y, Fujii H

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

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 VEGF(165). 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).

Published 24 January 2008 in Oncology, 72(3): 172-80.
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