MMP-7 is upregulated by COX-2 and promotes proliferation and invasion of lung adenocarcinoma cells

Abstract

Matrix metalloproteinases (MMPs) have been implicated in a variety of pathophysiological conditions, of which MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin. However, the function of MMP-7 in human lung adenocarcinoma (LAC) is unclear. In the present study the expression of MMP-7 in LAC was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects and molecular mechanisms of lentiviral vector-mediated MMP-7 siRNA (siMMP-7) on cell proliferation and invasive potential in LAC A549 cells, measured by MTT and Transwell assays, respectively. It was found that, the expression of MMP-7 protein in LAC was significantly increased compared with that in adjacent non-cancerous tissues (ANCT) (76.0% vs 44.0%, P<0.001), and positively correlated with lymph node metastases of the tumor (P=0.014). Furthermore, targeted inhibition of cyclooxygenase-2 (COX-2) by siRNA downregulated the expression of MMP-7 and inhibited invasion of LAC cells, and knockdown of MMP-7 suppressed tumor proliferation and invasion in LAC cells. Taken together, our findings indicate that increased expression of MMP-7 is associated with lymph node metastasis and upregulated by COX-2, and promotes the tumorigenesis of LAC, suggesting that MMP-7 may be a potential therapeutic target for the treatment of cancer.

Keywords

• MMP-7, COX-2, lung adenocarcinoma