title: Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer.
abstract: OBJECTIVE
  The molecular basis of cell motility is highly complex and is controlled by a number of molecular systems, whereas angiogenesis is an important biological component of tumor progression. The aims of this study were to investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and to identify the cell surface molecules involved in gastrointestinal tumors.
  
  
  METHODS
  We addressed these issues using functional monoclonal antibodies, which inhibit cell motility, endothelial cell migration, and tube formation. Furthermore, we investigated the relationship between this antigen and colon cancer, and showed the prognostic significance in human colon cancer.
  
  
  RESULTS
  We established a murine monoclonal antibody MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kilodalton protein, and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13 expression was associated with tumor status (P = 0.025). The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients with negative APN/CD13 expression tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression.
  
  
  CONCLUSIONS
  Our data suggest that APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression may be a useful indicator of a poor prognosis for node-positive patients with colon cancer.
authors.affiliation: Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hashida
authors.forename: Arimichi
authors.initials: A
authors.lastname: Takabayashi
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Kanai
authors.forename: Masashi
authors.initials: M
authors.lastname: Adachi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kondo
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyake
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003110:Colonic Neoplasms / Q000401:mortality* / Q000503:physiopathology; D018076:DNA, Complementary / Q000032:analysis; D018572:Disease-Free Survival; D000939:Epitopes / Q000276:immunology; D005354:Fibrosarcoma / Q000401:mortality* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000401:mortality / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D000939:Epitopes; D018826:CD13 Antigens