Establishment and long-term xenografting of human pancreatic carcinomas in immunosuppressed mice: changes and stability in morphology, DNA ploidy and proliferation activity

Abstract

The prognosis of pancreatic carcinoma is grave, therefore the experimental model systems remain major tools for testing new treatment modalities. We have developed human pancreatic cancer lines growing in immunosuppressed mice and characterized them by morphological and flow-cytometric studies. Immunosuppression has been achieved in young (4-week-old) CBA/CA mice by thymectomy, whole-body irradiation and bone marrow reconstruction. Twelve surgically removed human pancreatic carcinomas were implanted subcutaneously and serially transplantable xenografts have been established. Altogether 129 samples derived from 59 generations have been analyzed. Out of 12 carcinomas, 6 developed continuously growing and transplantable xenografts (PZX-2, PZX-5, PZX-11, PZX-15, PZX-16, PZX-20; take rate: 50%). They were successfully maintained for 9–16 passages, for 18–25 months. New subpopulations developed during transplantations in 3 tumor lines and these morphological changes have been reflected by the appearance of an aneuploid peak in flow cytometry. In 1 tumor line, however, DNA aneuploidy was observable despite the unaltered histology. The PZX-20 line retained its original morphology and aneuploid pattern during 9 consecutive passages and over 18 months. The results indicate that the artificially immunosuppressed CBA/CA mice are suitable hosts for accepting and maintaining human pancreatic carcinomas. During successive xenograftings the regular morphological characterization must be supplemented by flow cytometry, because new tumorous clones may develop despite the unchanged histological picture.