Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation.
We have investigated the effect of monoclonal antibodies (MAbs) specific for aminopeptidase N/CD13 on the invasion of human metastatic tumor cells into reconstituted basement membrane (Matrigel). The invasion of human metastatic tumor cells (SN12M renal-cell carcinoma, HT1080 fibrosarcoma and A375M melanoma) into Matrigel-coated filters was inhibited by an anti-CD13 MAb, WM15, in a concentration-dependent manner. However, this MAb did not have any effect on tumor-cell adhesion and migration to the extracellular matrices, which may be involved in tumor-cell invasion. MAb WM15 inhibited the degradation of type-IV collagen by tumor cells in a concentration-dependent manner. We also found that WM15 inhibited hydrolysing activities towards substrates of aminopeptidases in 3 different tumor cells. Since our previous study indicated that bestatin, an aminopeptidase inhibitor, was able to inhibit tumor-cell invasion, as well as aminopeptidase activities of murine and human metastatic tumor cells, cell-surface amino-peptidase N/CD13 may be partly involved in the activation mechanism for type-IV collagenolysis to achieve tumor-cell invasion, and anti-CD13 MAb WM15 may inhibit tumor-cell invasion through a mechanism involving its inhibitory action on the aminopeptidase N in tumor cells.
Saiki
I
I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Fujii
H
H
Yoneda
J
J
Abe
F
F
Nakajima
M
M
Tsuruo
T
T
Azuma
I
I
D000626:Aminopeptidases / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D018826:CD13 Antigens; D002448:Cell Adhesion; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000626:Aminopeptidases; D018826:CD13 Antigens