Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer.
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.
Hashida
Hiroki
H
Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
Takabayashi
Arimichi
A
Kanai
Michiyuki
M
Adachi
Masashi
M
Kondo
Keiichi
K
Kohno
Nobuoki
N
Yamaoka
Yoshio
Y
Miyake
Masayuki
M
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
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D000939:Epitopes; D018826:CD13 Antigens