title: Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer.
abstract: BACKGROUND
  Scirrhous gastric cancer is associated with peritoneal dissemination and advanced lymph node metastasis from an early stage, and the prognosis is still poor. In this study, we aimed to analyze candidate molecules for targeted therapy of scirrhous gastric cancer. We searched for molecules/metabolic activity that might be predominantly expressed in a subpopulation of scirrhous gastric cancer cells and might function as cancer stem cell markers.
  
  
  RESULTS
  For this purpose, we investigated the expression of various cell surface markers and of aldehyde dehydrogenase (ALDH) activity. These analyses showed that the scirrhous gastric cancer cell lines HSC-58 and HSC-44PE heterogeneously expressed CD13, while CD44, CDCP1, EpCAM and ABCG2 were expressed uniformly. Moreover, 10% of the total HSC-58 cell population expressed ALDH enzyme activity. A subpopulation of cells strongly positive for ALDH also expressed high levels of CD13, both of which are known as cancer stem cell markers. HSC-58 cells expressing high levels of CD13 showed lower sensitivity to a cancer drug cisplatin than cells with low levels of CD13. In contrast, CD13(-high) subpopulation of HSC-58 was more sensitive to an aminopeptidase N inhibitor bestatin. In terms of antibody-drug therapy, anti-CD13-immunotoxin was highly cytotoxic towards HSC-58 cells and was more cytotoxic than anti-EpCAM-immunotoxin.
  
  
  CONCLUSIONS
  These data suggest that CD13 is a suitable cell surface candidate for targeted antibody-drug therapy of scirrhous gastric cancer.
authors.affiliation: Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nohara
authors.affiliation: Department of Biomedical Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan; Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: kzkatou@juntendo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujiwara
authors.affiliation: Department of Biomedical Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakuragi
authors.affiliation: Division of Translational Research, Exploratory Oncology and Clinical Trial Center, National Cancer Center Hospital East, 6-5-1 Kashiwano-ha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwanuma
authors.affiliation: Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kajiyama
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D018826:CD13 Antigens / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000922:Immunotoxins; D000444:Aldehyde Dehydrogenase; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex; D002945:Cisplatin