Establishment and characterization of novel xenograft models of human biliary tract carcinomas.
Authors:Emura F, Kamma H, Ghosh M, Koike N, Kawamoto T, Saijo K, Ohno T, Ohkohchi N, Todoroki T.
Abstract:In order to develop new therapeutic regimens for biliary tract cancers, which carry dismal prognoses, the establishment of a human biliary tract cancer xenograft model is essential. Herein, we report the successful establishment and characterization of two xenograft models of human biliary tract cancers. An adenosquamous gallbladder cancer cell line (TGBC-44) and a bile duct adenocarcinoma cell line (TGBC-47) were obtained from fresh surgical specimens in our department and subcutaneously inoculated into nude mice. The overall tumor take rate was 100% and solid tumors grew measurable after 5 and 7 days for TGBC-44 and TGBC-47, respectively. Tumor doubling time was 3.9+/-1.1 and 4.1+/-0.5 days in the exponential growth phase in TGBC-44 and TGBC-47 xenografts, respectively. Isozyme test and karyotype analysis confirmed the human origin. Histopathology analysis revealed that the TGBC-44 xenograft retained both the squamous and the adenocarcinoma components, and the TGBC-47 xenograft exhibited poorly differentiated adenocarcinoma as in the corresponding original tumors. Immunohistochemistry and Western blotting studies revealed positive and similar expression of platelet derived endothelial growth factor/thymidine phosphorylase (PDGF/TP), thymidylate synthase (TS), and cyclooxygenase-2 (COX-2) in both original tumors and xenograft models. No macroscopic metastases were found at the time of sacrifice. We have successfully established two models of human biliary tract cancer, gallbladder and bile duct cancer. Models retained the morphological and biochemical characteristics of the original tumor and demonstrated constant biological behavior in all transplanted mice. These models could be useful tools for developing new diagnostic and therapeutic strategies against biliary tract cancers.