M.W. Roomi, J.C. Monterrey, T. Kalinovsky, A. Niedzwiecki and M. Rath
Oncology Reports 2009; 22(6):1283-1291

Abstract:
Matrix metalloproteinases (MMPs) secreted by lung cancer (LC) and malignant mesothelioma (MM), especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, and inhibitors on MMP-2 and MMP-9 expression in LC and MM cell lines. Human LC (A-549) and MM (MSTO-211H) cell lines were cultured in appropriate media.

At near confluence, the cells were washed with PBS and incubated in serum- free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. LC expressed MMP-2, whereas MM expressed MMP-2 and MMP-9. TNF-, IL-1, LPS, and PMA stimulated MMP-2 in LC and inhibited MMP-2 in MM. Doxycycline, EGCG and NM inhibited MMP–2 and MMP–9 expression, in both cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 in both cancer cell lines and inhibited MMP-9 in MM. Our results show that cytokines and inhibitors have an up- or down-regulatory effect on MMP-2 and MMP-9 expression in LC and MM, suggesting the clinical value of targeting these proteases for the management of LC and MM and their pathogenesis.

The full study is available online at:
http://www.spandidos-publications.com/or/22/6/1283