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. 2006 Jul 17;54(1):137–143. doi: 10.1002/ijc.2910540122

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

Ikuo Saiki 1,✉, Junya Yoneda 1, Ichiro Azuma 1, Hideji Fujii 2, Fuminori Abe 2, Motowo Nakajima 3, Takashi Tsuruo 3
PMCID: PMC7165932  PMID: 8097496

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‐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.

References

  1. Amoscato, A. A. , Stamkoski, R. M. , Babcock, G. F. and Alexander, J. W. , Neutral surface aminopeptidase activity of human tumor cell lines. Biochem. biophys. Acta, 1041, 317–319 (1990). [DOI] [PubMed] [Google Scholar]
  2. Ashmun, R. A. and Look, A. T. , Metalloproteinase activity of CD13/ aminopeptidase N on the surface of human myeloid cells. Blood, 75, 462–469 (1990). [PubMed] [Google Scholar]
  3. Bruley‐Rosset, M. , Florentin, I. , Kinger, N. , Schulz, J. and Mathe, G. , Restoration of impaired immune functions of aged animals by chronic bestatin treatment. Immunology, 38, 75–83 (1979). [PMC free article] [PubMed] [Google Scholar]
  4. Chop, A. M. , Nakajima, M. and Nicolson, G. L. , Metastatic mammary adenocarcinoma cell lines expressed elevated levels of plasma membrane cathepsin H‐like and aminopeptidase‐like activities. Proc. Amer. Ass. Cancer Res., 30, 98 (1989). [Google Scholar]
  5. Delmas, B. , Geefi, J. , L'Haridon, R. , Vogel, K. L. , Sjostrom, H. , Noren, O. and Laude, H. , Aminopeptidase N is a major receptor for the entropathogenic coronavirus TGEV. Nature (Land.), 357, 417–420 (1992). [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fidler, I. J. , Gersten, D. M. and Hart, I. R. , The biology of cancer invasion and metastases. Advanc. Cancer Res., 28, 149–250 (1978). [DOI] [PubMed] [Google Scholar]
  7. Gorvel, J.‐F. , Vivier, I. , Naquet, P. , Brekelmans, P. , Rigal, A. and Pierres, M. , Characterization of the neutral aminopeptidase activity associated to the mouse thymocyte‐activating molecules. J. Immunol., 144, 2899–2907 (1990). [PubMed] [Google Scholar]
  8. Kuramochi, H. , Motegi, A. , Iwabuchi, M. , Takahashi, K. , Horinishi, H. and Umezawa, H. , Action of ubenimex on aminopeptidase activities in spleen cells and peritoneal macrophages from mice. J. Antibiotics, 40, 1605–1611 (1987). [DOI] [PubMed] [Google Scholar]
  9. Liotta, L. A. , Abe, S. , Gehron, P. R. and Martin, G. R. , Preferential digestion of membrane collagen by an enzyme derived from metastatic tumor. Proc. nat. Acad. Sci. (Wash.), 76, 2268–2272 (1979). [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liotta, L. A. , Goldfarb, R. H. , Brundage, R. , Siegal, G. K. , Terranova, V. and Garbsia, S. , Effect of plasminogen activator (urokinasc), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res., 41, 4629–4636 (1981). [PubMed] [Google Scholar]
  11. Liotta, L. A. , Rao, C. V. and Barsky, S. H. , Tumor invasion and the extracellular matrix. Lab. Invest., 49, 639–649 (1983). [PubMed] [Google Scholar]
  12. Liotta, L. A. , Tryggvason, K. , Garbisa, S. , Hart, I. , Foltz, C. M. and Shafie, S. , Metastatic potential correlates with enzymatic degradation of basement‐membrane collagen. Nature (Loud.), 284, 67–68 (1980). [DOI] [PubMed] [Google Scholar]
  13. Look, T. A. , Ashmun, R. A. , Shapiro, L. H. and Peipfr, S. C. , Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J. clin. Invest., 83, 1299–1307 (1989). [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McCarthy, J. B. , Basara, M. L. , Palm, S. L. , Sas, D. F. and Furcht, L. T. , The role of cell‐adhesion proteins—laminin and fibronectin—in the movement of malignant and metastatic cells. Cancer Metast. Rev., 4, 125–152 (1985). [DOI] [PubMed] [Google Scholar]
  15. Morahan, P. S. , Edelson, P. J. and Grass, K. , Changes in macrophages ectoenzymes associated with anti‐tumor activity. J. Immunol., 125, 1312–1317 (1980). [PubMed] [Google Scholar]
  16. Moscatelli, D. and Rifkin, D. B. , Membrane and matrix localization of proteinases—a common theme in tumor‐cell invasion and angiogenesis. Biochem. biophys. Acta, 948, 67–85 (1988). [DOI] [PubMed] [Google Scholar]
  17. Murata, J. , Saiki, I. , Yoneda, J. and Azuma, I. , Differences in chemotaxis to fibronectin in low‐ and high‐metastatic tumor cells. Jap. J. Cancer Res., 83, 1327–1333 (1992). [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Naito, S. , Walker, S. M. and Fidler, I. J. , In vivo selection of human renal‐cell carcinoma cells with high metastatic potential in nude mice. Clin. exp. Metast., 7, 381–389 (1989). [DOI] [PubMed] [Google Scholar]
  19. Nakajima, M. and Chop, A. M. , Tumor invasion and extracellular matrix degradative enzymes: regulation of activity by organ factors. Semin. Cancer Biol., 2, 115–127 (1991). [PubMed] [Google Scholar]
  20. Nakajima, M. , Welch, D. R. , Belloni, P. N. and Nicolson, G. L. , Degradation of basement‐membrane type‐IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clone of differing metastatic potentials. Cancer Res., 47, 4869–4876 (1987). [PubMed] [Google Scholar]
  21. Nicolson, G. L. , Tumor‐cell instability, diversification, and progression to the metastatic phenotype' from oncogene to oncofetal expression. Cancer Res., 47, 1473–1487 (1987). [PubMed] [Google Scholar]
  22. Nicolson, G. L. , Metastatic tumor‐cell interactions with endothelium, basement membrane and tissue. Curr. Opinion Cell Biology, 1, 1009–1019 (1989). [DOI] [PubMed] [Google Scholar]
  23. Saiki, I. , Iida, J. , Murata, J. , Ogawa, R. , Nishi, N. , Sugimura, K. , Tokura, S. and Azuma, I. , Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequence of cell‐adhesive molecules. Cancer Res., 49, 3815–3822 (1989a). [PubMed] [Google Scholar]
  24. Saiki, I. , Murata, J. , Watanabe, K. , Fujii, H. , Abe, F. and Azuma, I. , Inhibition of tumor‐cell invasion by ubenimex (bestatin) in vitro. Jap. J. Cancer Res., 80, 873–878 (1989b). [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saito, K. , Takegoshi, K. , Aoyaoi, T. , Umezawa, H. and Nagai, Y. , Stimulatory effect of bestatin, a new specific inhibitor of aminopeptidase, on the blastogenesis of guinea‐pig lymphocytes. Cell Immunol., 40, 242–262 (1978). [DOI] [PubMed] [Google Scholar]
  26. Schorlemmer, H.‐U. , Bosslet, K. and Sedlacek, H. H. , The ability of the immunomodulating dipeptide bestatin to activate cytotoxic mono‐nuclear phagocytes. Cancer Res., 43, 4148–4153 (1983). [PubMed] [Google Scholar]
  27. Talmadge, J. E. , Lenz, B. F. , Pennington, R. , Long, C. , Philips, H. , Schneider, M. and Tribble, H. , Immunomodulatory and therapeutic properties of bestatin in mice. Cancer Res., 46, 4505–4510 (1986). [PubMed] [Google Scholar]
  28. Tryggvason, K. , Hoyhtya, M. and Salo, T. , Proteolytic degradation of extracellular matrix in tumor invasion. Biochem. biophys. Acta, 907, 191–217 (1987). [DOI] [PubMed] [Google Scholar]
  29. Wachsmuth, E. D. , Aminopeptidase as a marker for macrophage differentiation. Exp. Cell Res., 96, 409–412 (1975). [DOI] [PubMed] [Google Scholar]
  30. Yeager, C. L. , Ashmun, R. A. , William, R. K. , Cardellichio, C. B. , Shapiro, L. H. , Look, A. T. and Holmes, K. V. , Human aminopeptidase N is a receptor for human coronavirus 229E. Nature (Lond.), 357, 420–422 (1992). [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoneda, J. , Saiki, I. , Fujii, H. , Abl, F. , Kojima, Y. and Azuma, I. , Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin). Clin. exp. Metastasis, 10, 49–59 (1992). [DOI] [PubMed] [Google Scholar]

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