骨肉瘤组织中HIF-1α、iNOS与GLUT-1的表达及其与血管生成的关系

Relationship between the expression of HIF-1α、iNOS and GLUT-1 and angiogenesis in osteosarcoma

背景与目的缺氧诱导因子-1α(HIF-1α)、诱导型一氧化氮合酶(iNOS)及葡萄糖转运蛋白-1(GLUT-1)是恶性肿瘤重要的相关因子。本实验研究三者在骨肉瘤组织中的表达,并探讨三者之间的相关性以及在骨肉瘤血管生成中的作用。方法采用免疫组织化学S-P法,检测64例骨肉瘤和10例瘤旁正常骨组织、6例骨纤维结构不良中HIF-1α、iNOS及GLUT-1蛋白的表达,同时用CD34标记血管内皮细胞,计算微血管密度(MVD)。结果64例骨肉瘤组织中HIF-1α蛋白阳性表达率为57.8%(37/64),与对照组12.5%(2/16)相比差异有非常显著性(P<0.01),iNOS和GLUT-1的蛋白阳性表达率分别为71.9%(46/64)和73.4%(47/64),亦显著高于对照组(18.81%和25.0%)(P<0.01);HIF-1α与iNOS表达一致符合率为76.6%(49/64),HIF-1α与GLUT-1表达一致符合率为71.9%(46/64),表达呈显著相关(P<0.05),且与瘤组织分期显著相关(P<0.05)。MVD平均值为21±8,HIF-1α与iNOS均阳性的骨肉瘤组织中MVD值明显高于两者均为阴性者,两者相比较差别有非常显著性(P<0.01)。结论骨肉瘤组织存在HIF-1α、iNOS及GLUT-1蛋白的阳性表达率高,三者在骨肉瘤的发生、发展过程中可能具有重要作用,HIF-1α与iNOS对促进骨肉瘤血管新生可能具有协同作用。

Background and purpose： HIF-1α,iNOS and GLUT-1 are all considered as important related factors in a variety of malignant tumors. We investigated the expression of HIF-1α,iNOS and GLUT-1 and their possible roles in the angiogenesis of osteosarcoma. Methods： HIF-1α,iNOS and GLUT-1 protein expressions were detected by immunohistochemical methods in the samples of 64 cases with osteosarcomas, 10 cases of normal bone and 6 cases of osteofibrous dysplasia, and the vascular endothelial cells were labeled with CD34 and the micro-vascular density（MVD） was assessed. Resuits： The positive expression rates of HIF-1α ,iNOS and GLUT-1 were 64% （41/64）, 70.3% （45/64） and 60.9% （ 39/ 64） in 64 cases of osteosarcoma, there were significant differences in terms of the expression of HIF-1α,iNOS and GLUT-1 between osteosarcoma and the other groups; The correlated expression of HIF-1α with either iNOS or GLUT-1 were 60.9% （39/64） and 57.8% （37/64）, respectively. Furthermore, the expressions of HIF-1α,iNOS and GLUT-1 were significantly associated with the stage of the tumor. The medium MVD was 21 ± 8, but MVD was much higher in tumors with positive expression of HIF-1α and iNOS than that in tumors with negative expression of both （P 〈 0. 05）. Conclusions： HIF-1α, iNOS and GLUT-1 are overexpressed in osteosarcoma, those proteins may play important roles in the genesis and development of osteosarcoma, HIF-1α and iNOS may have synergistic effect in angiogenesis of osteosarcoma.