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  • 杨庆诚,曾炳芳*,张智长,施忠民,董扬.低氧诱导因子1α在骨肉瘤中的表达及其与血管生成的相关性[J].第二军医大学学报,2008,29(5):0504-0508    [点击复制]
  • YANG Qing-cheng,ZENG Bing-fang*,ZHANG Zhi-chang,SHI Zhong-min,DONG Yang.Expression of HIF-1α and its relationship with angiogenesis in osteosarcoma[J].Acad J Sec Mil Med Univ,2008,29(5):0504-0508   [点击复制]
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低氧诱导因子1α在骨肉瘤中的表达及其与血管生成的相关性
杨庆诚,曾炳芳*,张智长,施忠民,董扬
0
(上海交通大学附属第六人民医院骨科,上海 200233)
摘要:
目的:探讨低氧诱导因子1α(HIF-1α)在骨肉瘤中的表达及其与肿瘤血管生成的关系。方法:低氧及模拟低氧条件下体外培养MG-63骨肉瘤细胞,另外收集30例骨肉瘤组织石蜡标本及20例新鲜冷冻骨肉瘤组织标本,采用RT-PCR、Western印迹、ELISA及免疫组织化学等方法,分别检测骨肉瘤细胞及组织中HIF-1α及其靶基因血管内皮生长因子(VEGF)的mRNA及蛋白表达,并计算微血管密度(MVD)。结果:在低氧及模拟低氧条件下,MG-63骨肉瘤细胞HIF-1α的mRNA表达无明显变化,但蛋白表达明显增加,而VEGF的mRNA、蛋白表达都增加(P<0.05)。20例新鲜骨肉瘤组织中HIF-1α mRNA总表达率为90%,VEGF mRNA总表达率为100%,均明显高于瘤旁组织(P<0.05)。HIF-1α、VEGF蛋白在骨肉瘤石蜡组织中阳性表达率分别为86.7%、93.3%,明显高于瘤旁组织的6.7%、26.7%(P<0.05)。Spearman等级相关分析HIF-1α蛋白表达与MVD明显相关(P=0.005,r=0.767),VEGF蛋白表达与MVD正相关(P<0.002,r=0.701)。结论:骨肉瘤中存在HIF-1α的高表达,可能与肿瘤血管生成相关;HIF-1α高表达可能提示骨肉瘤患者预后不良。
关键词:  骨肉瘤  低氧诱导因子1α;血管生成
DOI:10.3724/SP.J.1008.2008.00504
投稿时间:2007-12-17修订日期:2007-12-17
基金项目:上海交通大学医学院博士点基金(BXJ0631).
Expression of HIF-1α and its relationship with angiogenesis in osteosarcoma
YANG Qing-cheng,ZENG Bing-fang*,ZHANG Zhi-chang,SHI Zhong-min,DONG Yang
(Department of Orthopedics,Shanghai Sixth People’s Hospital,Shanghai Jiaotong University,Shanghai 200233,China)
Abstract:
Objective:To investigate the expression of HIF-1α and its relationship with angiogenesis in osteosarcoma. Methods: Osteosarcoma MG-63 cells were cultured in vitro under hypoxia and mimic hypoxia conditions.Thirty paraffin-embedded osteosarcoma tissues and 20 fresh frozen osteosarcoma specimens were collected.The mRNA and protein expression of HIF-1α and VEGF were detected by RT-PCR,Western blotting,ELISA,and immunohistochemistry methods.The mean vessel density(MVD) were also calculated.Results: The mRNA level of HIF-1α had no change under hypoxia and minic hypoxia conditions,whereas the protein expression was increased dramaticaly.The mRNA and protein expression of VEGF was significantly increased under hypoxia and minic hypoxia conditions.The positive rate of HIF-1α mRNA (90%) and VEGF(100%) in 20 fresh frozen tissues were higher than those of the para-tumor tissues(P<0.05).The positive rates of HIF-1α and VEGF protein in paraffin-embedded osteosarcoma were 86.7% and 93.3%, respectively, significantly higher than those in the para-tumor tissues (6.7%,26.7%,P<0.05).Spearman related analysis demonstrated that the expression of HIF-1α(P=0.005,r=0.767) and VEGF(P<0.002,r=0.701) had a positive relation with MVD.Conclusion: HIF-1α is overexpressed in osteosarcoma and might be closely associated with tumor angiogenesis.Overexpression of HIF-1α might indicate a poor prognosis of osteosarcoma.
Key words:  osteosarcoma  hypoxia-inducible factor-1α  angiogenesis