乳腺癌中肿瘤相关巨噬细胞STAT3激活与多种细胞因子及预后因素有关  

STAT3 activation of tumor-associated macrophages is associated with various cytokines and prognostic factors in breast cancer

作　　者：孙正魁[1] 刘胜春[2] 姚榛祥[2] 

机构地区：[1]江西省肿瘤医院乳腺外科,南昌330029 [2]重庆医科大学附属第一医院普外科,重庆400016

出　　处：《肿瘤》2009年第1期65-68,共4页Tumor

基　　金：重庆市科委自然科学基金资助项目(编号:CSTC2007BB5261)

摘　　要：目的:探讨乳腺癌中肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)信号转导与转录激活子3(signal trans-ducer and activators of transcription 3,STAT3)的信号激活和局部细胞因子(IL-1β、TNF-α、TGF-β和IL-12)以及乳腺癌预后因素的关系。方法:免疫组织化学法检测50例乳腺癌组织、15例正常乳腺组织中的巨噬细胞浸润密度,采用转录因子DNA结合ELISA法检测其中33例乳腺癌组织中TAMs的STAT3 DNA结合活性,并用ELISA法检测肿瘤组织中IL-1β、TNF-α、TGF-β和IL-12含量,分析TAMs的STAT3 DNA结合活性与IL-1β、IL-12、TNF-α、TGF-β含量及临床病理参数的关系。结果:乳腺癌组织中巨噬细胞浸润密度明显高于正常乳腺组织。与外周血单核-巨噬细胞比较,TAMs的STAT3 DNA结合活性增高(P=0.007)。乳腺癌组织中TAMs的STAT3活性与IL-1β、TNF-α、TGF-β含量呈正相关(P=0.036、P=0.008、P=0.005),与IL-12含量呈负相关(P=0.002)。而且肿瘤分级高或CerbB-2阳性患者TAMs的STAT3活性较高(P=0.043、P=0.013)。结论:乳腺癌中TAMs的STAT3信号激活与肿瘤组织中IL-1β、TNF-α、TGF-β含量增加和IL-12含量降低有关,与肿瘤分级和CerbB-2状态有关。Objective ： To investigate the correlation of signal transducer and activators of transcription 3 （ STAT3 ） activation of tumor-associated macrophages （TAMs） with local cytokines （IL-1β, TNF-α, TGF-β, and IL-12） and prognostic factors in breast cancer. Methods： Infiltration density of TAMs was detected by immunohistoehemistry in 50 primary breast cancers and 10 normal breast tissues. STAT3-DNA binding activity of TAMs in 33 out of 50 primary breast cancers was measured by transcription factor DNA-binding ELISA. In addition, the concentrations of IL-1 β, TNF-α, TGF-β, and IL-12 in the cultured 33 primary breast cancers were measured by ELISA. The correlation of STAT3 activity of TAMs with the concentrations of IL-1β, TNF-α, TGF-β, and IL-12 was analyzed. The relationship between STAT3 activity of TAMs and clinicopathologic parameters was also evaluated. Results： The TAMs density was significantly higher in primary breast cancers than that in normal breast tissues. STAT3 DNA-binding activity of TAMs in breast cancer patients was significantly higher than that of monocytes/macrophages from peripheral blood （ P = 0. 007 ）. STAT3 activity of TAMs had positive correlation with the levels of IL-1β, TNF-α, and TGF-β （ P = 0.036, P = 0. 008, P =0. 005 ） , but had negative correlation with the level of IL-12 （P = 0. 002）. STAT3 activity of TAMs was higher in CerbB-2 positive breast cancer patients and highly graded breast cancer patients（P = 0. 043 ,P = 0. 013 ）. Conclusions： STAT3 activation of TAMs may be associated with increased levels of IL-1β, TNF-α, and TGF-β and decreased level of IL-12 in breast cancer. STAT3 activation of TAMs was related with histological grade and CerbB-2 status of breast cancer patients.

关 键 词：乳腺肿瘤 巨噬细胞 STAT3转录因子 细胞因子类 预后 

分 类 号：R737.9[医药卫生—肿瘤]