Clinical & Experimental Metastasis

, Volume 17, Issue 10, pp 857–863

Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines

  • Akira Kido
  • Sabine Krueger
  • Carsten Haeckel
  • Albert Roessner
Article

DOI: 10.1023/A:1006794617406

Cite this article as:
Kido, A., Krueger, S., Haeckel, C. et al. Clin Exp Metastasis (1999) 17: 857. doi:10.1023/A:1006794617406

Abstract

This study aimed at clarifying the role of Aminopeptidase N (APN), a Zn2+-dependent ectopeptidase localized on the cell surface of human osteosarcoma cell lines treated with proinflammatory cytokines. We investigated the proinflammatory cytokines interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) as well as the anti-inflammatory cytokine transforming growth factor beta (TGF-β) for their influence on APN regulation. Soluble IL-6 receptor (sIL-6R) was always used together with IL-6 to achieve a stable effect. In addition, the invasive potential of the osteosarcoma cell lines MG63 and HOS was examined. Competitive RT-PCR and Ala-pNA activity assays revealed that IL-6 and sIL-6R significantly increased the mRNA expression and activity of APN in both osteosarcoma cell lines. Although IL-1β significantly stimulated APN mRNA expression in both cell lines, it influenced the enzyme activity only in MG63. TNF-α and TGF-β, however, had an effect neither on mRNA expression nor on the enzyme activity of APN in both cell lines. In the Matrigel invasion assay, IL-6 and sIL-6R significantly up-regulated the transmigration of these cell lines, whereas other cytokines did not. The up-regulated invasion was inhibited by bestatin, a specific inhibitor of APN. Cellular migration correlated highly with APN activity (r = 0.79, P < 0.002). These findings suggest that APN contributes to the invasive potential of human osteosarcomas enhanced by IL-6 and SIL-6R.

aminopeptidase Ninterleukin-6invasionmatrigelosteosarcoma

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Akira Kido
    • 1
  • Sabine Krueger
    • 1
  • Carsten Haeckel
    • 1
  • Albert Roessner
    • 1
  1. 1.Department of PathologyOtto-von-Guericke UniversityMagdeburgGermany