Establishment and long-term xenografting of human pancreatic carcinomas in immunosuppressed mice: changes and stability in morphology, DNA ploidy and proliferation activity
Establishment and long-term xenografting of human pancreatic carcinomas in immunosuppressed mice: changes and stability in morphology, DNA ploidy and proliferation activity
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DOI：
10.1007/s004320050236
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发表时间：
1999-01-01
影响因子：
3.6
通讯作者：
Zalatnai, A
中科院分区：
文献类型：
--
作者：
Bocsi, J;Zalatnai, A
胰腺癌的预后很严重，因此实验模型系统仍然是测试新治疗方式的主要工具。我们开发了在免疫抑制小鼠中生长的人类胰腺癌细胞系，并通过形态学和弓形细胞计数研究对其进行了表征。通过胸腺切除术、全身照射和骨髓重建，在年轻（4 周龄）CBA/CA 小鼠中实现了免疫抑制。将十二个手术切除的人类胰腺癌皮下植入，并建立了可连续移植的异种移植物。总共分析了来自 59 个世代的 129 个样本。在 12 种癌症中，有 6 种出现持续生长和可移植的异种移植物（PZX-2、PZX-5、PZX-11、PZX-15、PZX-16、PZX-20；采用率：50%）。它们成功维持了 9-16 代，持续 18-25 个月。在 3 个肿瘤系的移植过程中形成了新的亚群，这些形态学变化已通过流式细胞术中非整倍体峰的出现反映出来。然而，在 1 个肿瘤系中，尽管组织学未改变，但仍可观察到 DNA 非整倍性。 PZX-20 系在 9 个连续传代和超过 18 个月的时间里保留了其原始形态和非整倍体模式。结果表明，人工免疫抑制的CBA/CA小鼠是接受和维持人胰腺癌的合适宿主。在连续的异种移植过程中，必须通过流式细胞术补充常规形态学特征，因为尽管组织学图片未改变，但可能会出现新的肿瘤克隆。
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 Bow-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.