Down-regulation of heparanase leads to the inhibition of invasion and proliferation of A549 cells in vitro and in vivo.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.