Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.
OBJECTIVE
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.


METHODS
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-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC.


CONCLUSIONS
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.
First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
Kousaku
K
Mimura
Koji
K
Kono
Mitsuhiko
M
Hanawa
Mirei
M
Kanzaki
Atsuhito
A
Nakao
Akishi
A
Ooi
Hideki
H
Fujii
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005784:Gene Amplification / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D053781:Transforming Growth Factor beta2; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D000068878:Trastuzumab; C509041:TGFB2 protein, human