Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines

Abstract

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 24 h 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-1ß, LPS and PMA, stimulated MMP-2 in LC and inhibited MMP-2 in MM, but had no effect on MMP-9. 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 downregulatory effect on MMP-2 and MMP-9 expression in LC and MM, suggesting the clinical value of targeting these proteases for management of LC and MM and their pathogenesis.

Evaluation of Anti-cancer and Pro-apoptotic Activities of Iranian Green Tea Extract Against A549,PC3, and MCF-7 Cancer Cell Lines

“…32 From in vitro studies, it was found that EGCG inhibited MMP-2 and -9 expressions in human lung cancer A549 cells. 33 Additionally, an inhibitory effect of EGCG on the migration of bronchial tumor cells in 2D and 3D cell culture models has been shown. EGCG treatment also inhibited the expression of MMP-2 in both mRNA and protein levels and altered the intermediate filaments of vimentin.…”

Cancer Salt Nostalgia

“…A chronically inflamed microenvironment can be induced either by reactive oxygen/nitrogen species (ROS/RNS) [ 18 ], paracrine factors, or tumor-infiltrating cells, inciting continuous cell proliferation, DNA damage, or cancer transformation [ 19 ]. Inflammatory cytokines [ 20 , 21 , 22 ] and chemokines [ 23 , 24 , 25 ] provide conducive signaling to induce cancer proliferation [ 20 , 26 ] and tumor angiogenesis [ 17 ]. It is well-established that salt induces a chronic inflammatory response [ 27 , 28 ].…”

Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review

“…Some other studies investigating MMPs in mesothelioma focused on the basic roles of MMPs in tumor invasion and progression [18,19]. Doi et al investigated the expression of MT1-MMP and the invasion ability of the mesothelioma cell line established from a clinical specimen of a patient with mesothelioma.…”