Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation

Saiki, Ikuo; Yoneda, Junya; Azuma, Ichiro; Fujii, Hideji; Abe, Fuminori; Nakajima, Motowo; Tsuruo, Takashi

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‐CD 13 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 aminopeptidase 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.