Heparanase participates in the growth and invasion of human U-2OS osteosarcoma cells and its close relationship with hypoxia-inducible factor-1 alpha in osteosarcoma

Although the expression of heparanase is associated with invasion and metastasis of various human cancers, the effects of heparanase on human osteosarcoma have not been evaluated. We showed that down-regulating the expression of heparanase significantly reduced proliferation and invasion of human U-2OS osteosarcoma cells. Furthermore, heparanase silencing by short-hairpin RNA (shRNA) was associated with decreased hypoxia-inducible factor-1 alpha (HIF-1 alpha) level, implying that heparanase was associated with the expression of HIF-1 alpha. This result was confirmed by immunohistochemistry analysis. In osteosarcoma tissues, immunohistochemical results revealed that heparanase expression had a close correlation with that of HIF-1 alpha and they had a strong relation with presence of pulmonary metastasis (P<0.05). Heparanase-positive samples had higher microvessel density (MVD) than heparanase-negative samples. Similarly, compared with HIF-1 alpha-negative samples, HIF-1 alpha-positive samples had higher MVD. Therefore, heparanase and HIF-1 alpha facilitated tumor angiogenesis and promoted pulmonary metastasis of osteosarcoma.