乳腺癌肿瘤相关巨噬细胞中HIF-2α/EPAS1表达与血管生成的关系  

Relationship between hypoxia-inducible factor-2α(HIF-2α)/endothelial PAS domain protein1(EPAS1) expression in tumor-associated macrophages and tumor angi

作　　者：郝汉霞[1] 王水[1] 刘力嘉[1] 范萍[1] 杜青[1] 张伟民[1] 王聪[1] 

机构地区：[1]南京医科大学第一附属医院普外科,江苏南京210029

出　　处：《中华肿瘤防治杂志》2006年第3期169-172,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家十五攻关课题(2001BA703B20);江苏省卫生系统重点人才基金(135工程)

摘　　要：目的:研究乳腺癌组织中血管生成的定量分析及与肿瘤相关巨噬细胞(TAMs)中低氧诱导因子-2α(HIF-2α)表达的相关性,探讨TAMs中HIF-2α表达对肿瘤间质血管生成的作用机制及对肿瘤生物学行为的影响。方法:应用免疫组化SP法检测60例乳腺癌组织中微血管密度(MVD)、血管内皮细胞生长因子(VEGF)、TAMs及TAMs中低氧诱导因子-2α(HIF-2α)的分布,并进行定量和相关性分析。结果:乳腺癌组织中微血管分布于肿瘤生长活跃的间质中。VEGF在正常的乳腺组织及癌组织均有表达,分布弥散。癌组织及癌周明显高于正常组织(P=0·006,P=0·013),以癌间质最高。TAMs在肿瘤组织内形态呈多样化,分布不均,以癌间质最高;HIF-2α在肿瘤细胞及TAMs中均有表达,但在癌组织及癌周TAMs中明显高于正常组织。TAMs中HIF-2α的表达与VEGF及MVD呈显著正相关(r=0·488,P=0·000;r=0·401,P=0·002)。结论:乳腺癌TAMs在肿瘤微环境中可能促进HIF-2α呈过量表达,并与VEGF及MVD显著相关,其表达在肿瘤微环境中具有促进肿瘤血管生成作用,且影响肿瘤的生物学行为。OBJECTIVE.. To investigate the relationship between HIF-2α/EPAS1 expression in TAMs and tumor angiogenesis and progression in human breast cancer. METHODS： The expression of HIF-2α/EPAS1 in TAMs, microvessel density （MVD） and vascular endothelial growth factor （VEGF） were investigated immunohistochemically on paraffin-embedded sections from 60 patients with breast cancer. RESULTS： MVD,VEGF and TAMs were highly expressed in breast cancer than in the normal tissue （P = 0. 006, P = 0. 013）, especially in the peri-cancerous tissues. HIF-2α/EPAS1 expression was restricted to either tumor cells or TAMs, and its expression in TAMs of adjacent mammary tissues was significantly higher than that in the control group. A correlation was found between high TAM HIF-2α and high VEGF （r=0. 488,P=0. 000）, and MVD, r=0. 401, P= 0. 002. CONCLUSIONS.. It suggests that the overexpression of TAM HIF-2α is significantly associated with the angiogenesis in human breast cancer. The mechanism may be that the elevated level of TAM HIF-2α induces the tumor angiogenesis by activating the transcription of VEGF gene. HIF-2α signaling may be a useful target in future antiangiogenic strategies.

关 键 词：乳腺肿瘤/病理学 巨噬细胞 内皮生长因子 缺氧 新生血管化 病理性 免疫组织化学 

分 类 号：R737.9[医药卫生—肿瘤]