Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines
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 Zn
2+-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 N interleukin-6 invasion matrigel osteosarcoma
This revised version was published online in July 2006 with corrections to the Cover Date.
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