Monoclonal antibody to HER-2/neu receptor enhances radiosensitivity of esophageal cancer cell lines expressing HER-2/neu oncoprotein.
OBJECTIVE
The role of HER-2/neu in the response of esophageal cancer to radiation is not well known. The purpose of this study was to evaluate the effect of an anti-HER-2/neu antibody trastuzumab on the proliferation, cell cycle distribution, and radiosensitivity of esophageal cancer cell lines.


METHODS
Expression of HER-2/neu protein by four esophageal squamous cancer cell lines (KE4, TE8, TE9, and TE10) and an esophageal adenocarcinoma cell line (SKGT4) was assessed using immunohistochemical (IHC) analysis and flow cytometry. We also evaluated HER-2/neu oncogene expression by fluorescence in situ hybridization. As a control for HER-2/neu protein expression and gene amplification, breast cancer cell lines (MCF7, MDA MB175VII, and SKBR3) were also examined. The cytotoxity of trastuzumab (0.1-200 microg/mL) was estimated by the MTT assay, and the cell cycle distribution was determined by flow cytometry. The effect of 10 microg/mL trastuzumab combined with radiation was assessed by a clonogenic assay.


RESULTS
Flow cytometry and IHC revealed that two esophageal cancer cell lines (TE9 and SKGT4) showed HER-2/neu expression (IHC 1+ and mean fluorescence intensity of 11-20), while the other esophageal cancer cell lines were negative for HER-2/neu expression. Although trastuzumab alone had no effect on the esophageal cancer cell lines, the combination of 10 microg/mL trastuzumab with radiation showed a synergistic effect on the HER-2/neu expressing cell lines.


CONCLUSIONS
This study suggested that trastuzumab plus irradiation may be effective for the treatment of esophageal cancers, including adenocarcinoma and squamous cell cancer with HER-2/neu expression.
Sato
Shinsuke
S
Department of Gastrointestinal Surgery, Juntendo University School of Medicine, Tokyo, Japan. ssato@maz.miinet.or.jp
Kajiyama
Yoshiaki
Y
Sugano
Masahiko
M
Iwanuma
Yoshimi
Y
Sonoue
Hiroshi
H
Matsumoto
Toshiharu
T
Sasai
Keisuke
K
Tsurumaru
Masahiko
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011838:Radiation-Sensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab