口腔鳞癌中STAT3的表达和肿瘤相关巨噬细胞含量的相关性分析
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摘要
目的:研究信号传导与转录激活因子3(STAT3)及肿瘤相关巨噬细胞(TAMs)与人口腔鳞状细胞癌发生、浸润、转移的关系及机制。方法:采用免疫组化的方法检测42例人口腔鳞状细胞癌和15例正常口腔粘膜组织中STAT3、CD68+(巨噬细胞标记物)、CD163+(M2型巨噬细胞标记物)的表达及浸润数量并探讨3者与临床病理指标之间的关系。结果:口腔鳞癌中STAT3的表达,CD68+、CD163+细胞的浸润数量与正常组比较明显高于正常组(P<0.05);癌组织中STAT3的阳性表达与分化、临床分期、有无淋巴结转移有关(P<0.05),但与患者年龄、性别无关; STAT3的表达与CD163+细胞浸润数呈正相关(r=0.397,P<0.05),CD68+和CD163+细胞在中、低分化中的浸润数量明显高于高分化组(P<0.05); CD68+与CD163+之间呈正相关(r=0.329,P=0.034)。结论:STAT3表达可能与肿瘤恶性程度相关,其高表达可能使巨噬细胞更多向M2形转化,而M2型巨噬细胞可能促进OSCC的浸润转移。
Objective:To investigate the Correlation between STAT3 expression and tumor associated macrophage content in oral squamous cell carcinoma.Methods:The expression and infiltration of STAT3,CD68+(Macrophage marker) and CD163+(M2 macrophage marker) in 42 cases of human oral squamous cell carcinoma and 15 cases of normal oral mucosa were detected by immunohistochemical method.Results:The expression of STAT3,the number of CD68+and CD163+cells in oral squamous cell carcinoma were significantly higher than those in normal group(P<0.05).The positive expression of STAT3 was related to differentiation,clinical stage and lymph node metastasis(P<0.05),but not related to age and sex.The expression of STAT3 had positive correlation with the number of CD163+cell infiltration(r=0.397,P<0.05).The infiltration of CD68+and CD163+cells in the middle and low differentiation group was significantly higher than that in the highly differentiated group(P<0.05).CD68+had positive correlation with CD163+(r=0.329,P=0.034).Conclusion:The expression of STAT3 may be related to the degree of malignancy of the tumor,and its high expression may lead to more M2-shaped transformation of macrophages,while M2 macrophages may promote the infiltration and metastasis of OSCC.
Objective:To investigate the Correlation between STAT3 expression and tumor associated macrophage content in oral squamous cell carcinoma.Methods:The expression and infiltration of STAT3,CD68+(Macrophage marker) and CD163+(M2 macrophage marker) in 42 cases of human oral squamous cell carcinoma and 15 cases of normal oral mucosa were detected by immunohistochemical method.Results:The expression of STAT3,the number of CD68+and CD163+cells in oral squamous cell carcinoma were significantly higher than those in normal group(P<0.05).The positive expression of STAT3 was related to differentiation,clinical stage and lymph node metastasis(P<0.05),but not related to age and sex.The expression of STAT3 had positive correlation with the number of CD163+cell infiltration(r=0.397,P<0.05).The infiltration of CD68+and CD163+cells in the middle and low differentiation group was significantly higher than that in the highly differentiated group(P<0.05).CD68+had positive correlation with CD163+(r=0.329,P=0.034).Conclusion:The expression of STAT3 may be related to the degree of malignancy of the tumor,and its high expression may lead to more M2-shaped transformation of macrophages,while M2 macrophages may promote the infiltration and metastasis of OSCC.
引文
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[16]ZHAO M,GAO F H,WANG J Y,et al.JAK2/STAT3signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and b FGF in non-small-cell lung cancer.[J].Lung Cancer,2011,73(3):366-374.
[17]GORDZIEL C,BRATSCH J,MORIGGL R,et al.Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma[J].British Journal of Cancer,2013,109(1):138.
[18]杨越.衰老巨噬细胞中IL-10激活的STAT3信号促进病理性眼球血管生成[J].生理科学进展,2016,47(03):210.
[19]HUGHES R,QIAN B Z,ROWAN C,et al.Perivascular M2 macrophages stimulate tumor relapse after chemotherapy[J].Cancer Research,2015,75(17):3479-3491.
[2]GERMANO G,FRAPOLLI R,BELGIOVINE C,et al.Role of macrophage targeting in the antitumor activity of trabectedin[J].Cancer Cell,2013,23(2):249-262.
[3]MANTOVANI A,GERMANO G,MARCHESI F,et al.Cancer-promoting tumor-associated macrophages:New vistas and open questions[J].European Journal of Immunology,2011,41(9):2522-2525.
[4]YUKIE T,HIROAKI T,KANAKO K,et al.Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer[J].Cancer Science,2016,107(8):1101-1109.
[5]YAO Y,YE H,QI Z,et al.B7-H4(B7x)-mediated cross-talk between glioma-initiating cells and macrophages via the il6/jak/stat3 pathway lead to poor prognosis in glioma patients[J].Clinical Cancer Research An Official Journal of the American Association for Cancer Research,2016,22(11):2778.
[6]GRANDIS J R,DRENNING S D,ZENG Q,et al.Constitutive activation of STAT3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo[J].Proc Natl Acad Sci U S A,2000,97(8):4227-4232.
[7]RODVOLD J J,ZANETTI M.Tumor microenvironment on the move and the Aselli connection.[J].Science Signaling,2016,9(434):fs13.
[8]Junttila M R,de Sauvage F J.Influence of tumour microenvironment heterogeneity on therapeutic response[J].Nature,2013,501(7467):346.
[9]KOMOHARA Y,JINUSHI M,TAKEYA M.Clinical significance of macrophage heterogeneity in human malignant tumors[J].Cancer Sci,2014,105(1):1-8.
[10]QIAN B Z,POLLARD J W.macrophage diversity enhances tumor progression and metastasis[J].Cell,2010,141(1):39.
[11]HERRERA A,DOMNGUEZ G,et al.Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients[J].Cancer Science,2013,104(4):437-444.
[12]SICA A,MANTOVANI A.Macrophage plasticity and polarization:in vivo veritas[J].Journal of Pathology,2012,229(2):176-185.
[13]RHEE I.Diverse macrophages polarization in tumor microenvironment[J].Archives of Pharmacal Research,2016:1-9.
[14]HUANG C,JIANG T,ZHU L,et al.STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo[J].International Journal of Oncology,2011,38(6):1637.
[15]SHIRAISHI D,FUJIWARA Y,KOMOHARA Y,et al.Glucagon-like peptide-1(GLP-1)induces M2 polarization of human macrophages via STAT3 activation[J].Biochemical and biophysical research communications,2012,425(2):304-308.
[16]ZHAO M,GAO F H,WANG J Y,et al.JAK2/STAT3signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and b FGF in non-small-cell lung cancer.[J].Lung Cancer,2011,73(3):366-374.
[17]GORDZIEL C,BRATSCH J,MORIGGL R,et al.Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma[J].British Journal of Cancer,2013,109(1):138.
[18]杨越.衰老巨噬细胞中IL-10激活的STAT3信号促进病理性眼球血管生成[J].生理科学进展,2016,47(03):210.
[19]HUGHES R,QIAN B Z,ROWAN C,et al.Perivascular M2 macrophages stimulate tumor relapse after chemotherapy[J].Cancer Research,2015,75(17):3479-3491.