Abstract
Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in tissue regeneration and organogenesis. However, its role in cancer remains unclear. We show here that fibulin-3 was silenced by hypermethylation of the promoter region in the relatively invasive A549 non-small cell lung cancer (NSCLC) cells compared with less invasive H460 NSCLC cells. Enforced expression of fibulin-3 in A549 cells down-regulated cellular MMP-7 and MMP-2, which was followed by inhibition of cell invasiveness. Conversely, suppression of fibulin-3 expression with siRNA in H460 cells showed the opposite effect. These results indicate that fibulin-3 is a negative regulator of invasiveness in NSCLC and further studies are needed for its therapeutic applications in treatment of NSCLC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Culture Media, Conditioned / pharmacology
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DNA Methylation*
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Extracellular Matrix Proteins / genetics*
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Extracellular Matrix Proteins / metabolism
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Extracellular Matrix Proteins / pharmacology
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Gene Expression Regulation, Neoplastic*
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism*
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Matrix Metalloproteinase 7 / genetics
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Matrix Metalloproteinase 7 / metabolism*
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Neoplasm Invasiveness
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Promoter Regions, Genetic*
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Signal Transduction
Substances
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Culture Media, Conditioned
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EFEMP1 protein, human
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Extracellular Matrix Proteins
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MMP7 protein, human
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Matrix Metalloproteinase 7
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MMP2 protein, human
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9