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

Abstract

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.

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on endothelial tumor cells, including malignancies of lung; gastric, colon and cervical carcinomas; gliomas and melanomas (Danhier et al, 2010;Genís et al, 2006). Aminopeptidase N/CD13, a metalloproteinase that eliminates amino-acids from unblocked N-terminal segments of peptides or proteins, is an endothelial cell-surface receptor involved in tumorcell invasion, extracellular matrix degradation by tumor cells and tumor metastasis in vitro and in vivo (Saiki et al, 1993;Danhier et al, 2010). NGR (Asn-Gly-Arg) peptide is reported to bind to the aminopeptidase (Pasqualini et al, 2000;Danhier et al, 2010).…”

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

“…Chemoinvasion assay was carried out by the method of Saiki et al (22). The lower and upper sides of 8 μm porosity polycarbonate filters were coated with 0.5 mg/ml type I collagen and 0.5 mg/ml Matrigel, respectively.…”

The Expression and Localization of Neutral Endopeptidase 24.11/CD10 in Human Gestational Trophoblastic Diseases

“…Increased expression of NEP in hepatocellular carcinoma has also been reported to be correlated with malignant transformation (Dragovic et al, 1994). Similarly, over-expression of APN/CD13 was directly involved in tumor invasion of renal cell cancer and melanoma (Fujii et al, 1995;Saiki et al, 1993) or in tumor proliferation of choriocarcinoma (Ino et al, 1994). Our recent studies have shown the upregulated expression of APA in choriocarcinoma and invasive cervical cancer (Fujimura et al, 2000).…”