整合素αvβ3在白细胞介素-8介导的雌激素受体阴性乳腺癌细胞侵袭及肿瘤血管生成中的作用  

Roles of integrin αvβ3 in interleukln-8-mediated metastasis and angiogenesis of estrogen receptornegative breast cancer cells

作　　者：李李[1] 邵楠[1] 叶润仪[1] 李杰[1] 王深明[1] 林颖[1] 

机构地区：[1]中山大学附属第一医院乳腺病诊治中心,广州510080

出　　处：《中华实验外科杂志》2013年第4期658-660,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金资助项目（S2012010011133）

摘　　要：目的探讨白细胞介素（IL）-8和整合素αvβ3在雌激素受体（ER）阴性乳腺癌细胞侵袭和肿瘤血管生成过程中的相互作用和关系。方法通过肿瘤细胞侵袭、黏附实验及血管内皮增殖、毛细血管管腔生成实验观察在IL-8介导的乳腺癌细胞侵袭及肿瘤血管生成中的作用。应用组织芯片技术，通过免疫组织化学法检测104例乳腺癌患者标本验证IL-8及αvβ3表达与ER的关系。结果IL-8组BT-549及MDA-MB-231细胞侵袭、黏附的细胞数显著高于对照组（P〈0.05）,而在IL-8＋αvβ3抗体组显著低于IL-8处理组（P 〈0.01） ;MCF-7在3组中侵袭和黏附的细胞数差异无统计学意义（P〉 0.05）。人脐静脉内皮细胞（HUVEC）在24、48、72h对照组中增殖速度显著低于IL-8组（P〈0．01），IL-8＋αvβ3抗体组较IL-8组增殖速度显著降低（P〈0．01）。与对照组比较，IL-8组中HUVEC更易形成类血管样的管状结构排列;而经过αVβ3抗体处理后HUVEC形成的管状结构减少。检测104例乳腺癌标本在IL-8阳性组和阴性组的表达率分别为62. 1%和32. 0%（P〈0. 01），其中ER阳性乳腺癌αvβ3的表达率分别为40. 0%和26. 1% （P 〉 0. 05）;而ER阴性乳腺癌组织αvβ3的表达率为73.7%和41.4%（P〈0.05）。结论ER阴性人乳腺癌细胞株中IL-8促进乳腺癌侵袭和肿瘤血管生成的作用可能与整合素αvβ3有关;IL-8和αvβ3在乳腺癌组织中的表达呈正相关，且与ER状态有关。Objective To identify the role of integin αvβ3 in interleukin （IL）-8-mediated metas-tasis and angiogenesis of breast cancer cells. Methods IL-8 and neutralizing antibody of integrin αvβ3were used in invasion and human umbilical vein endothelial cells （ HUVECs） -tumor cells adhesion assay toobserve the changes of metastasis of breast cancer cells. Proliferation assay and angiogenesis of HUVECscultured with IL-8 and antibody of αvβ3 were applied to evaluate the effect of αvβ3 on IL-8-mediated an-giogenesis. The correlation between IL-8 and αvβ3 expression was examined by using immunohistochemis-try, and relationship between the expression of IL-8 and αvβ3 with estrogen receptor （ER） status in pa-tients was further analyzed. Results . IL-8 significantly inhanced the migration of ER negative breast cancercell lines BT-549 and MDA-MB-231 as compared with those cultured with phosphate buffer （ PBS, P 〈0.05）. After the addition of antibody of αvβ3 , the number of BT-549 and MDA-MB-231 cells culturedwith IL-8 was declined significantly （P 〈0. 01）,whereas IL-8 had no effect on ER positive breast cancercell line MCF-7 （p 〉0.05）. Proliferation of HUVECs cultured with IL-8 was markedly promoted （ P 〈0. 01 ）,which could be blocked by antibody of αvβ3 （ P 〈 0. 01 ）. HUVECs cultured with IL-8 tended toform more microangioid structure, and suppression of angiogenesis could be observed after the addition ofantibody of αvβ3. In the 104 breast cancer specimens, 62. 1% showed positive αvβ3 expression in theIL-8 positive group, which was significantly higher than that in IL-8 negative group （P 〈0. 01 ） . In addi-tion ,the expression of αvβ3 was correlated with IL-8 in ER-negative breast cancer cells （P 〈 0. 05）. Con-clusion Integrin αvβ3 may be involved in metastasis and angiogenesis of ER-negative breast cancer cellspromoted by IL-8. The expression of αvβ3 correlates with IL-8 expression, which is related to ER status.

关 键 词：乳腺肿瘤 雌激素受体 白细胞介素-8 整合素ΑVΒ3 

分 类 号：R737.9[医药卫生—肿瘤]