胰腺癌细胞起源和演进的新实验证据  

Novel evidences of cell origin and progression in pancreatic ductal adenocarcinoma

作　　者：郭俊超[1] 赵玉沛[1] Dale E.Bockman 廖泉[1] Michael W.Muller Helmut Friess 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院基本外科,北京市100730 [2]Department of General Surgery,University of Heidelberg,Germany

出　　处：《中华肝胆外科杂志》2005年第5期320-323,共4页Chinese Journal of Hepatobiliary Surgery

摘　　要：目的大量研究证实导管样复合体就是胰腺癌的前体病变,因此,本研究旨在探索植入致癌剂后胰腺癌前体病变的产生和发展。方法采用手术方法将致癌剂DMBA植入SD大鼠胰腺,从第1天开始,在不同的时间点获取胰腺进行组织学研究,同时,分别以糜蛋白酶和细胞角蛋白作为胰腺腺泡细胞和导管细胞的标记物,通过免疫组化方法进行定位。结果在包埋致癌剂第2天就可以观察到正常胰腺小叶向导管复合体移型的现象,第4天出现典型的导管复合体,同时,胰岛也参与了这一过程。小叶中的非导管细胞迅速转分化为导管细胞的特征。在1个月时观察到导管腺癌的形成。与对照组相比,腺泡-导管转分化过程在DMBA包埋组持续存在。结论胰腺癌前体病变(导管复合体)除了由已经存在于小叶内的导管细胞组成外,主要通过腺泡细胞转分化形成,同时,胰岛细胞在某种程度上也参与了导管复合体的形成。因此,胰腺腺泡细胞、胰岛细胞和导管细胞共同参与了胰腺导管腺癌前体细胞的起源,转分化可以不需要细胞分裂迅速发生,而恶性转化需要较长的时间。Objective To identify the changes that produce the precursor lesions immediately after implantation of carcinogen and investigate their development.Methods Animals were sacrificed at intervals beginning from the 1st d after implantation of carcinogen and the pancreas was histologically examined.Chymotrypsin and cytokeratin were immunocytochemically localized as markers for acinar and ductal cells.Results Transition of lobules to tubular complexes began by 2 d after implantation of carcinogen.Within 4 d after the implantation,well-developed tubular complexes were present.Islets participated in the process.The transition occurred in an environment of necrosis and apoptosis,edema,and inflammation.Non-duct cells in lobules quickly took on the characteristics of duct cells.Ductal adenocarcinoma was observed as early as in 1 month after the implantation.Acino-ductal transdifferentiation persisted in DMBA-implanted animals but not in controls.Conclusions The precursor lesions(tubular complexes) are formed by the transdifferentiation of acinar cells and some islet cells,with the incorporation of duct cells pre-existing in the lobules.Therefore,cells that at one time are acinar cells,islet cells and duct cells provide the precursor cells for the ductal adenocarcinoma developing from tubular complexes.Transdifferentiation,which does not require cell division,occurs rapidly.Transformation to cancer takes longer.

关 键 词：胰腺癌 细胞起源 胰腺腺泡细胞 导管细胞 证据 实验 演进 免疫组化方法 DMBA 导管腺癌 胰岛细胞 复合体 用手术方法 组织学研究 细胞角蛋白 细胞转分化 致癌剂 SD大鼠 糜蛋白酶 正常胰腺 持续存在 分化过程 细胞组成 前体细胞 

分 类 号：R735.9[医药卫生—肿瘤] R733.1[医药卫生—临床医学]