Please wait a minute...

中国现代手术学杂志  2017, Vol. 21 Issue (2): 85-89    DOI: 10.16260/j.cnki.1009 -2188.2017.02.002
  手术学研究 |
肿瘤相关巨噬细胞和细胞因子表达对三阴乳腺癌患者预后的影响
王建国,李绍杰
湖南省湘潭市中心医院普外科,湘潭411100
The Expression of Tumor Associated Macrophages and Cytokines in the Triple-negative Breast Cancer Patients after the Surgery
WANG Jian-guo,LI Shao-jie
Department of General Surgery,The Central Hospital of Xiangtan,Xiangtan 411100,Hunan,China
下载:  RICH HTML  PDF (911KB) 
输出:  BibTeX | EndNote (RIS)      
摘要 目的 探讨三阴性乳腺癌(triple-negative breast cancer,TNBC))患者肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)和细胞因子表达对患者预后的影响。方法应用免疫组织化学(IHC)、S-P染色法检测肿瘤相关巨噬细胞(TAMs)在48例TNBC样本标记CD68的表达,对关键的细胞因子包括IL-6、IL-10、IL-12、IL-1β,趋化因子(C-C motif)ligand-5(ccl-5)和巨噬细胞炎性蛋白-2(MIP-2)进行定量RT-PCR和酶联免疫吸附试验(ELISA)。结果34例(70.8%)TNBC样本有CD68阳性表达。低浸润组(14例)和高浸润组(20例)比较显示,高浸润组ccl-5和IL-6的表达均显著上调(P<0.01),而其它细胞因子表达水平比较无统计学差异。高浸润组生存率较低浸润组低(P<0.05)。结论大多数TNBC患者术后TAMs表达上调,提示预后不良,尤其是高浸润组。那些有更多巨噬细胞的肿瘤,细胞因子IL-6和趋化因子ccl-5也有高表达,两者有潜能成为TNBC的临床指标及药物靶点。
服务
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章
王建国,李绍杰
关键词:  乳腺癌,三阴性  肿瘤相关巨噬细胞  白细胞介素6  ccl-5    
Abstract: ObjectiveTo explore the expressional value of tumor associated macrophages(TAMs)and cytokines in the prognosis of triple-negative breast cancer(TNBC).MethodsImmunohistochemistry(IHC)and S-P staining method were used to detect the TAMs marker CD68 expression in 48 TNBC samples.Expressions of key cytokines including interleukin-6(IL-6),IL-10,IL-12,IL-1β,chemokine(C-C motif)ligand-5(CCL-5)and macrophage inflammatory protein-2(MIP-2)were quantified by RT-PCR and enzyme-linked immunosorbent assay(ELISA).The correlation between CD68 expression and prognosis was analyzed.Results34 cases(70.8%)out of 48 TNBC samples appeared CD68-positive expression.Compared to low infiltrated samples,IL-6 and CCL-5 were up-regulated in the high infiltrated tumors samples(P <0.01),but there was no statistical difference in other cytokines between low and high infiltrated tumor samples.The survival rate of high infiltrated tumor samples were lower than that of low infiltrated tumor sample(P <0.05).ConclusionsThe expression of TAMs were up-regulated in most of TNBC patients after the surgery.Its expression suggested unfavorable prognosis especially in high-infiltrated group.Those tumors with more macrophage also had elevated expression of cytokine(IL-6)and chemotactic factor(CCL-5),both of which have potency to be clinical index and drug target for TNBC.
Key words:  breast cancer,triple-negative    tumor-associated macrophages    interleukin-6    ccl-5
收稿日期:  2016-12-29      修回日期:  2017-04-13                发布日期:  2018-05-25      期的出版日期:  2017-04-26
ZTFLH:  R737.9  
通讯作者:  王建国   
作者简介:  王建国,男,40岁,湖南省湘潭市中心医院普外二(乳甲)科主任,副主任医师。
引用本文:    
王建国,李绍杰. 肿瘤相关巨噬细胞和细胞因子表达对三阴乳腺癌患者预后的影响[J]. 中国现代手术学杂志, 2017, 21(2): 85-89.
WANG Jian-guo,LI Shao-jie. The Expression of Tumor Associated Macrophages and Cytokines in the Triple-negative Breast Cancer Patients after the Surgery. Chinese Journal of Modern Operative Surgery, 2017, 21(2): 85-89.
链接本文:  
http://www.surgerychina.com/CN/10.16260/j.cnki.1009 -2188.2017.02.002  或          http://www.surgerychina.com/CN/Y2017/V21/I2/85
[1]Youlden DR,Cramb SM,Dunn NA,et al.The descriptive epidemiology of female breast cancer:an international comparison of screening,incidence,survival and mortality[J].Cancer Epidemiol,2012,36(3):237-248.doi:10.1016/j.canep.2012.02.007.|[2]Markkula A,Bromée A,Henningson M,et al.Given breast canc-er,does breast size matter?Data from a prospective breast cancer cohort[J].Cancer Causes Control,2012,23(8):1307-1316.doi:10.1007/s10552-012-0008-9.|[3]Creighton CJ,Li X,Landis M,et al.Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features[J].Proc Natl Acad Sci U S A,2009,106(33):13820-13825.doi:10.1073/pnas.0905718106.|[4]Hennessy BT,Gonzalez-Angulo AM,Stemke-Hale K,et al.Characterization of a naturally occurring breast cancer subset enriched inepithelial-to-mesenchymal transition and stem cell characteristics[J].Cancer Res,2009,69(10):4116-4124.doi:10.1158/0008-5472.CAN-08-3441.|[5]Evers B,Drost R,Schut E,et al.Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281and cisplatin[J].Clin Cancer Res,2008,14(12):3916-3925.doi:10.1158/1078-0432.CCR-07-4953.|[6]Markkula A,Hietala M,Henningson M,et al.Clinical profiles predict early nonadherence to adjuvant endocrine treatment in a prospective breast cancer cohort[J].Cancer Prev Res(Phila),2012,5(5):735-745.doi:10.1158/1940-6207.CAPR-11-0442.|[7]Lundin KB,Henningson M,Hietala M,et al.Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients[J].Br J Cancer,2011,105(11):1676-83.doi:10.1038/bjc.2011.441.|[8]Smith AK,Conneely KN,Pace TW,et al.Epigenetic changes associated with inflammation in breast cancer patientstreated with chemotherapy[J].Brain Behav Immun,2014,38:227-36.doi:10.1016/j.bbi.2014.02.010.|[9]Ambarus CA,Krausz S,van Eijk M,et al.Systematic validation of specific phenotypic markers for in vitro polarized humanmacrophages[J].J Immunol Methods,2012,375(1-2):196-206.doi:10.1016/j.jim.2011.10.013.|[10]Multhoff G,Radons J.Radiation,inflammation,and immune responses in cancer[J].Front Oncol,2012,2:58.doi:10.3389/fonc.2012.00058.eCollection 2012 Jun 4.|[11]Foulkes WD,Smith IE,Reis-Filho JS.Triple-negative breast cancer[J].N Engl J Med,2010,363(20):1938-1948.doi:10.1056/NEJMra1001389.|[12]Su S,Liu Q,Chen J,et al.A positive feedback loop between mesenchymal-like cancer cells andmacrophages is essential to breast cancer metastasis[J].Cancer Cell,2014,25(5):605-620.doi:10.1016/j.ccr.2014.03.021.|[13]Huang M,Wang L,Ma H,et al.Lack of an association between interleukin-6-174G/C polymorphism andcirculating interleukin-6 levels in normal population:a meta-analysis[J].DNA Cell Biol,2013,32(11):654-664.doi:10.1089/dna.2013.2148.|[14]Hudis CA,Gianni L.Triple-negative breast cancer:an unmet medical need[J].Oncologist,2011,16 Suppl 1:1-11.doi:10.1634/theoncologist.2011-S1-01.|[15]Tiainen S,Tumelius R,Rilla K,et al.High numbers of macrophages,especially M2-like(CD163-positive),correlate withhyaluronan accumulation and poor outcome in breast cancer[J].Histopathology,2015,66(6):873-83.doi:10.1111/his.12607.|[16]Stormes KA,Lemken CA,Lepre JV,et al.Inhibition of metastasis by inhibition of tumor-derived CCL5[J].Breast Cancer Res Treat,2005,89(2):209-212.|[17]Ferrari N,Mohammed ZM,Nixon C,et al.Expression of RUNX1 correlates with poor patient prognosis in triple negativebreast cancer[J].PLoS One,2014,9(6):e100759.doi:10.1371/journal.pone.0100759.eCollection 2014.|[18]Tyner JW,Bumm TG,Deininger J,et al.CYT387,a novel JAK2 inhibitor,induces hematologic responses and normalizesinflammatory cytokines in murine myeloproliferative neoplasms[J].Blood,2010,115(25):5232-5240.doi:10.1182/blood-2009-05-223727.|[19]Pardanani A,Laborde RR,Lasho TL,et al.Safety and efficacy of CYT387,a JAK1 and JAK2 inhibitor,in myelofibrosis[J].Leukemia,2013,27(6):1322-1327.doi:10.1038/leu.2013.71.|[20]Marotta LL,Almendro V,Marusyk A,et al.The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24-stemcelllike breast cancer cells in human tumors[J].J Clin Invest,2011,121(7):2723-2735.doi:10.1172/JCI44745.|[21]Tiezzi DG,Valejo FA,Marana HR,et al.CD44+/CD24-cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast[J].Med Oncol,2012,29(3):1479-1485.doi:10.1007/s12032-011-0014-x.|[22]Britschgi A,Andraos R,Brinkhaus H,et al.JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade:arationale for cotargeting these pathways in metastatic breast cancer[J].Cancer Cell,2012,22(6):796-811.doi:10.1016/j.ccr.2012.10.023.|[23]Thomas S,Baumgart DC.Targeting leukocyte migration and adhesion in Crohn's disease and ulcerativecolitis[J].Inflammopharmacology,2012,20(1):1-18.doi:10.1007/s10787-011-0104-6.|[24]Empana JP,Jouven X,CanouI-Poitrine F,et al.C-reactive protein,interleukin 6,fibrinogen and risk of sudden death in Europeanmiddle-aged men:the PRIME study[J].Arterioscler Thromb Vasc Biol,2010,30(10):2047-2052.doi:10.1161/ATVBAHA.110.208785.|[25]Anderson DR,Poterucha JT,Mikuls TR,et al.IL-6 and its receptors in coronary artery disease and acute myocardial infarction[J].Cytokine,2013,62(3):395-400.doi:10.1016/j.cyto.2013.03.020.
[1] 简文静, 唐静, 王先明. 12基因模型对乳腺导管原位癌复发风险预测的回顾性分析[J]. 中国现代手术学杂志, 2017, 21(3): 161-167.
[2] 王建国, 李绍杰.  

肿瘤相关巨噬细胞和细胞因子表达对三阴乳腺癌患者预后的影响 [J]. 中国现代手术学杂志, 2017, 21(2): 85-89.

No Suggested Reading articles found!
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed