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Cancer Therapy: Preclinical |
Authors' Affiliations: 1 First Department of Surgery, 2 First Department of Pathology, and 3 Department of Immunology, University of Yamanashi, Yamanashi, Japan
Requests for reprints: Koji Kono, First Department of Surgery, University of Yamanashi, 1110 Tamaho, Yamanashi 409-3898, Japan. Phone: 81-552-73-7390; Fax: 81-55-273-9574; E-mail: kojikono{at}yamanashi.ac.jp.
Purpose: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2–expressing esophageal SCC cell lines.
Experimental Design: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab.
Results: Trastuzumab induced ADCC against HER-2–expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-ß–producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-ß. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2–expressing esophageal SCC.
Conclusion: HER-2–expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.
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