G-CSF在结肠炎相关结直肠癌中的表达  

The expression of G-CSF in colitis-associated cancer

作　　者：石新英 袁伟[2] 唐万燕[2] 左雯[2] 徐玥[2] 钟儒刚[1] 马洁[2] 

机构地区：[1]北京工业大学生命科学与生物工程学院,北京100022 [2]中国医学科学院肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《癌症进展》2016年第2期168-171,174,共5页Oncology Progress

基　　金：国家重点基础研究发展计划(2014CB542103);北京市自然科学基金(7144237);科技北京百名领军人才培养工程(Z13110700513001);北京市科技新星计划(Z131107000413066)

摘　　要：目的探索粒细胞集落刺激因子(granulocyte-colony stimulating factor,G-CSF)在结肠炎相关结直肠癌小鼠模型中的表达情况,并研究小鼠结直肠部位G-CSF的细胞来源。方法利用致癌剂氧化偶氮甲烷(azoxymethane,AOM)和致炎剂葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导小鼠的结直肠癌,通过免疫组化方法检测G-CSF在炎症向肿瘤发展各阶段小鼠结直肠组织中的表达情况,利用免疫荧光方法检测小鼠结直肠部位与GCSF共定位的细胞。结果 AOM/DSS小鼠模型能良好地模拟结肠炎相关结直肠癌病程特点:本研究将其分为3个阶段,即AD1、AD2、AD3阶段。其中AD1阶段小鼠结直肠部位存在大量淋巴细胞的浸润,AD2阶段小鼠有不典型增生和腺瘤,AD3阶段小鼠结直肠出现原位癌病变。与正常小鼠相比,AD1、AD2、AD3阶段小鼠结直肠部位G-CSF表达升高,且AD2阶段表达水平最高;G-CSF与小鼠结直肠部位的上皮细胞共定位最广泛,只有少量的肌成纤维细胞和巨噬细胞能跟G-CSF共定位。结论本研究中AOM/DSS小鼠模型经历了正常黏膜→不典型增生→腺瘤→腺癌的发展过程,能够较好地模拟人由炎症性肠病逐步发展成结肠炎相关结直肠癌的病程;AD小鼠与正常小鼠相比表达较高水平的G-CSF,且AD2阶段G-CSF表达最高;AOM/DSS小鼠模型中,G-CSF主要由小鼠结直肠部位的上皮细胞分泌,部分巨噬细胞和肌成纤维细胞也可以产生G-CSF。Objective To investigate the expression of granulocyte-colony stimulating factor （G-CSF） in a mouse model of colitis-associated cancer （CAC）, and to study the cellular source of G-CSF in colorectum area. Method CAC in mouse model was induced by carcinogen azoxymethane （AOM） and pro-inflammatory agents dextran sodium sulfate （DSS）. The expression of G-CSF in the colorectum of normal and AD mice was examined by immunohistochemistry. The cellular source of G-CSF was investigated by immunofluorescence. Result AOM/DSS mouse model well simulated the characteristic pathological process of CAC, and was staged as AD1, AD2 and AD3 in our study. The colonrectum in AD1 mice suffered heavy infiltration of lymphocytes. AD2 mice had dysplasia and adenoma. AD3 mice appeared cancer in situ. AD mice had a higher expression level of G-CSF than normal mice, and the expression of G-CSF in AD2 mice was the highest. G-CSF was mainly co-localized with the intestinal epithelial cells of colorectum area, and only a few myofibroblasts and macrophages exhibited significant co-localization with G-CSF. Conclusion In this study, AOM/DSS mice underwent a typical development process of normal mucosa→hyperplasia→adenoma→adenocarcinoma, which is similar with the development of human CAC. The level of G-CSF in AD mice was higher than that of normal mice, and the ex- pression level of G-CSF in AD2 mice was the highest. In AOM/DSS mouse model, the major cellular source of G-CSF were intestinal epithelial cells, and a few myofibroblasts and macrophages can also produce G-CSF.

关 键 词：结肠炎相关结直肠癌 炎症性肠病 粒细胞集落刺激因子 

分 类 号：R735.3[医药卫生—肿瘤]