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MMP-7 is Upregulated by COX-2 and Promotes Proliferation and Invasion of Lung Adenocarcinoma Cells

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 M...

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Detalles Bibliográficos
Autores principales: Zhang, J., Luo, J., Ni, J., Tang, L., Zhang, H.P., Zhang, L., Xu, J.F., Zheng, D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980206/
https://www.ncbi.nlm.nih.gov/pubmed/24704993
http://dx.doi.org/10.4081/ejh.2014.2262
Descripción
Sumario: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.