Pour P M, Weide L, Liu G, Kazakoff K, Scheetz M, Toshkov I, Ikematsu Y, Fienhold M A, Sanger W
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, USA.
Am J Pathol. 1997 Jun;150(6):2167-80.
To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined had the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model.
为研究胰岛在胰腺癌发生中的作用，将刚分离的雄性叙利亚仓鼠胰岛移植到50只雌性仓鼠的右下颌下腺，这些雌性仓鼠有的用链脲佐菌素预处理过，有的未预处理。将甲状腺碎片、纤维素粉和永生的仓鼠胰腺导管细胞注入同一只仓鼠的左下颌下腺。然后，所有受体仓鼠每周接受强效胰腺癌致癌物N-亚硝基双（2-氧代丙基）胺治疗，剂量为40mg/kg体重，共3周。3至8周后，75只仓鼠中有18只（24%）在移植胰岛的下颌下腺区域发生了大导管型腺癌，但左下颌下腺均未发生肿瘤。18只仓鼠中有9只发生了多发性肿瘤，因此共发现31处癌症。其中11处癌位于移植胰岛附近，其中8处可见胰岛内导管或囊肿形成，如同仓鼠胰腺癌发生过程中胰腺所见。胰岛内导管结构的形成在体外也得到了证实。这些胰岛附近的一些肿瘤细胞与抗胰岛素抗体呈反应性。在检测的3处肿瘤中的1处通过聚合酶链反应分析发现了Y染色体信息。此外，与诱发的胰腺肿瘤一样，检测的3处下颌下腺肿瘤均在密码子12处发生了c-Ki-ras癌基因的突变，且所有肿瘤均表达A血型抗原。这些以及其他发现有力地表明，胰岛的某些成分，很可能是干细胞，是该模型中导管型腺癌的起源。
