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Fibulin-3, an extracellular glycoprotein, has been suggested as having functionsin tissue regeneration and organogenesis. However, its role in cancer remainsunclear. We show here that fibulin-3 was silenced by hypermethylation of the promoterregion in the relatively invasive A549 non-small cell lung cancer (NSCLC) cellscompared with less invasive H460 NSCLC cells. Enforced expression of fibulin-3in A549 cells down-regulated cellular MMP-7 and MMP-2, which was followed by inhibitionof cell invasiveness. Conversely, suppression of fibulin-3 expression with siRNAin H460 cells showed the opposite effect. These results indicate that fibulin-3is a negative regulator of invasiveness in NSCLC and further studies are neededfor its therapeutic applications in treatment of NSCLC.

Fibulin-3 promoter methylation alters the invasive behavior of non-small cell lung cancer cell lines via MMP-7 and MMP-2 regulation