胰腺癌细胞起源和演进的新实验证据

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，腺泡一导管转分化过程在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。

Novel evidences of cell origin and progression in pancreatic ductal adenocarcinoma

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.