Lung colonization of B16 mouse melanoma cells is inhibited following silencing (sM2 antiheparanase siRNA) of the heparanase gene. Both gene expression (A: RT-PCR) and lung metastasis (B, C) are inhibited by 80%–90% upon silencing of the endogenous heparanase gene, indicating a causal involvement of heparanase in tumor cell metastasis.