Heparanase participates in the growth and invasion of human U-2OS osteosarcoma cells and its close relationship with hypoxia-inducible factor-1α 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-1α (HIF-1α) level, implying that heparanase was associated with the expression of HIF-1α. This result was confirmed by immunohistochemistry analysis. In osteosarcoma tissues, immunohistochemical results revealed that heparanase expression had a close correlation with that of HIF-1α 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-1α-negative samples, HIF-1α-positive samples had higher MVD. Therefore, heparanase and HIF-1α facilitated tumor angiogenesis and promoted pulmonary metastasis of osteosarcoma.
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C Zen
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Department of Pathology, Sun Yat-sen University, Guang-dong, People's Republic of China.
Luo
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Yang
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Wang
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D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D049109:Cell Proliferation; D002648:Child; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis* / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D034622:RNA Interference; D000099175:Heparanase
D005966:Glucuronidase; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099175:Heparanase; C497442:HIF1A protein, human