肝细胞癌中M2巨噬细胞标志物与NF-κB p50相关性研究
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摘要
目的:探讨不同分期肝细胞癌病人组织中M2巨噬细胞及核因子κB (NF-κB)p50的表达情况,并分析其表达的相关性。方法:整群收集2012-2015年80例肝细胞肝癌病人和10例肝内胆管结石病人(对照组)的组织标本,采用免疫荧光双染法检测CD163和CD206的表达;收集2015年10月至2016年1月20例接受肝细胞癌手术病人的新鲜组织标本,采用Western blotting法检测不同分期的肝癌组织中CD163、CD206的表达及NF-κB p50的表达。结果:肝癌病人石蜡组织切片中CD163和CD206的共定位高于对照组,Ⅲ+Ⅳ期肝癌切片中的共定位高于Ⅰ+Ⅱ期;Western blotting结果表明,肝癌组织中CD163、CD206及NF-κB p50的表达高于癌旁组织(P<0.05～P<0.01),Ⅲ+Ⅳ期肝癌组织中的表达高于Ⅰ+Ⅱ期(P<0.01)。NF-κB p50与CD163、CD206的表达均呈正相关(r=0.963、0.944,P<0.01)。结论:随着肝癌进展,M2巨噬细胞数量和NF-κB p50的表达均升高,提示两者可能具有协同作用,共同促进肝癌进展。
Objective:To evaluate the expression of M2 macrophages and nuclear factor κB(NF-κB) p50 in patients with different stages of hepatocellular carcinoma(HCC),and analyze the relationship between them.Methods:The expression levels of CD163 and CD206 in 80 cases of paraffin sections of patients with HCC and 10 cases of patients with hepatolithiasis(control group) were detected.The expression levels of CD163,CD206 and NF-κB p50 in 20 cases of fresh liver tissues of patients with different stages of HCC were detected using Western blotting from October 2015 to January 2016.Results:The co-localization of CD163 and CD206 in paraffin section of HCC was higher than that in control group,and the co-localization of which in TNM Ⅲ+Ⅳ stage HCC was higher than that in TNM Ⅰ+Ⅱstage HCC.The results of Western blotting showed that the expression levels of CD163,CD206 and NF-κB p50 in hepatocellular carcinoma tissue were higher than those in para-carcinoma tissue(P<0.05 to P<0.01),and the expression levels of CD163,CD206 and NF-κB p50 in Ⅲ+Ⅳ stage hepatocellular carcinoma tissue were higher than those in Ⅰ+Ⅱ stage hepatocellular carcinoma tissue(P<0.05 to P<0.01).The expression of NF-κB p50 was positively correlated with the expressions of CD163 and CD206(r=0.963,r=0.944,P<0.01).Conclusions:With the development of liver tissue,the number of M2 macrophages and NF-κB p50 level increase,which suggest that the two may have synergistic effects to promote the progression of liver cancer.
Objective:To evaluate the expression of M2 macrophages and nuclear factor κB(NF-κB) p50 in patients with different stages of hepatocellular carcinoma(HCC),and analyze the relationship between them.Methods:The expression levels of CD163 and CD206 in 80 cases of paraffin sections of patients with HCC and 10 cases of patients with hepatolithiasis(control group) were detected.The expression levels of CD163,CD206 and NF-κB p50 in 20 cases of fresh liver tissues of patients with different stages of HCC were detected using Western blotting from October 2015 to January 2016.Results:The co-localization of CD163 and CD206 in paraffin section of HCC was higher than that in control group,and the co-localization of which in TNM Ⅲ+Ⅳ stage HCC was higher than that in TNM Ⅰ+Ⅱstage HCC.The results of Western blotting showed that the expression levels of CD163,CD206 and NF-κB p50 in hepatocellular carcinoma tissue were higher than those in para-carcinoma tissue(P<0.05 to P<0.01),and the expression levels of CD163,CD206 and NF-κB p50 in Ⅲ+Ⅳ stage hepatocellular carcinoma tissue were higher than those in Ⅰ+Ⅱ stage hepatocellular carcinoma tissue(P<0.05 to P<0.01).The expression of NF-κB p50 was positively correlated with the expressions of CD163 and CD206(r=0.963,r=0.944,P<0.01).Conclusions:With the development of liver tissue,the number of M2 macrophages and NF-κB p50 level increase,which suggest that the two may have synergistic effects to promote the progression of liver cancer.
引文
[1] LLOVET JM,ZUCMAN-ROSSI J,PIKARSKY E,et al.Hepatocellular carcinoma[J].Nat Rev Dis Primers,2016,2:16018.
[2] TORRE LA,BRAY F,SIEGEL RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65:87.
[3] BORZIO M,FORNARI F,DE SIO I,et al.Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma:results of an Italian field practice multicenter study[J].Future Oncol,2013,9(2):283.
[4] MANTOVANI A,ALLAVENA P,SICA A,et al.Cancer-related inflammation[J].Nature,2008,454(7203):436.
[5] GUARDIOLA AA,GOMEZ RR,ROMERO GM,et al.Characteristics and course of chronic hepatitis B e antigen-negative infection[J].Gastroenterol Hepatol,2017,40(2):59.
[6] INOUE T,TANAKA Y.Hepatitis B virus and its sexually transmitted infection - an update[J].Microb Cell,2016,3(9):420.
[7] SIA D,VILLANUEVA A,FRIEDMAN SL,et al.Liver cancer cell of origin,molecular class,and effects on patient prognosis[J].Gastroenterology,2017,152(4):745.
[8] SPANO D,ZOLLO M.Tumor microenvironment:a main actor in the metastasis process[J].Clin Exp Metastasis,2012,29(4):381.
[9] PAPP H,LASZLO B,JAKAB F,et al.Review of group A rotavirus strains reported in swine and cattle[J].Vet Microbiol,2013,165(3/4):190.
[10] LAWRENCE T,NATOLI G.Transcriptional regulation of macrophage polarization:enabling diversity with identity[J].Nat Rev Immunol,2011,11(11):750.
[11] REBELO SP,PINTO C,MARTINS TR,et al.3D-3-culture:a tool to unveil macrophage plasticity in the tumour microenvironment[J].Biomaterials,2018,163:185.
[12] WANG S,ZHANG J,SUI L,et al.Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis[J].Sci Rep,2017,7(1):14982.
[13] GONG H,ZULIANI P,KOMURAVELLI A,et al.Analysis and verification of the HMGB1 signaling pathway[J].BMC Bioinformatics,2010,11(Suppl 7):S10.
[14] SMALE ST.Hierarchies of NF-kappaB target-gene regulation[J].Nat Immunol,2011,12(8):689.
[15] PORTA C,IPPOLITO A,CONSONNI FM,et al.Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression[J].Cancer Immunol Res,2018,6(5):578.
[16] BISWAS SK,ALLAVENA P,MANTOVANI A.Tumor-associated macrophages:functional diversity,clinical significance,and open questions[J].Semin Immunopathol,2013,35(5):585.
[17] COOK J,HAGEMANN T.Tumour-associated macrophages and cancer[J].Curr Opin Pharmacol,2013,13(4):595.
[18] LEE H,HERRMANN A,DENG JH,et al.Persistently activated Stat3 maintains constitutive NF-κB activity in tumors[J].Cancer Cell,2009,15(4):283.
[19] PORTA C,RIMOLDI M,RAES G,et al.Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB[J].Proc Natl Acad Sci U S A,2009,106(35):14978.
[2] TORRE LA,BRAY F,SIEGEL RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65:87.
[3] BORZIO M,FORNARI F,DE SIO I,et al.Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma:results of an Italian field practice multicenter study[J].Future Oncol,2013,9(2):283.
[4] MANTOVANI A,ALLAVENA P,SICA A,et al.Cancer-related inflammation[J].Nature,2008,454(7203):436.
[5] GUARDIOLA AA,GOMEZ RR,ROMERO GM,et al.Characteristics and course of chronic hepatitis B e antigen-negative infection[J].Gastroenterol Hepatol,2017,40(2):59.
[6] INOUE T,TANAKA Y.Hepatitis B virus and its sexually transmitted infection - an update[J].Microb Cell,2016,3(9):420.
[7] SIA D,VILLANUEVA A,FRIEDMAN SL,et al.Liver cancer cell of origin,molecular class,and effects on patient prognosis[J].Gastroenterology,2017,152(4):745.
[8] SPANO D,ZOLLO M.Tumor microenvironment:a main actor in the metastasis process[J].Clin Exp Metastasis,2012,29(4):381.
[9] PAPP H,LASZLO B,JAKAB F,et al.Review of group A rotavirus strains reported in swine and cattle[J].Vet Microbiol,2013,165(3/4):190.
[10] LAWRENCE T,NATOLI G.Transcriptional regulation of macrophage polarization:enabling diversity with identity[J].Nat Rev Immunol,2011,11(11):750.
[11] REBELO SP,PINTO C,MARTINS TR,et al.3D-3-culture:a tool to unveil macrophage plasticity in the tumour microenvironment[J].Biomaterials,2018,163:185.
[12] WANG S,ZHANG J,SUI L,et al.Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis[J].Sci Rep,2017,7(1):14982.
[13] GONG H,ZULIANI P,KOMURAVELLI A,et al.Analysis and verification of the HMGB1 signaling pathway[J].BMC Bioinformatics,2010,11(Suppl 7):S10.
[14] SMALE ST.Hierarchies of NF-kappaB target-gene regulation[J].Nat Immunol,2011,12(8):689.
[15] PORTA C,IPPOLITO A,CONSONNI FM,et al.Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression[J].Cancer Immunol Res,2018,6(5):578.
[16] BISWAS SK,ALLAVENA P,MANTOVANI A.Tumor-associated macrophages:functional diversity,clinical significance,and open questions[J].Semin Immunopathol,2013,35(5):585.
[17] COOK J,HAGEMANN T.Tumour-associated macrophages and cancer[J].Curr Opin Pharmacol,2013,13(4):595.
[18] LEE H,HERRMANN A,DENG JH,et al.Persistently activated Stat3 maintains constitutive NF-κB activity in tumors[J].Cancer Cell,2009,15(4):283.
[19] PORTA C,RIMOLDI M,RAES G,et al.Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB[J].Proc Natl Acad Sci U S A,2009,106(35):14978.