Hotz H G, Reber H A, Hotz B, Foitzik T, Buhr H J, Cortina G, Hines O J
Department of Surgery, UCLA School of Medicine, Los Angeles, California, USA.
Pancreas. 2001 Mar;22(2):113-21. doi: 10.1097/00006676-200103000-00002.
The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.
胰腺癌（PaCa）的研究需要原位、具有临床相关性的动物模型。本研究的目的是在具有免疫活性的Lewis大鼠中建立导管胰腺腺癌的原位模型，并开发一种评分系统来量化局部肿瘤浸润和远处转移。将大鼠导管PaCa细胞系DSL-6A/C1的细胞（10⁷）皮下注射到供体大鼠体内。8周后，将由此产生的皮下肿瘤的三个（IPL-3）或五个（IPL-5）碎片（1立方毫米）显微手术植入受体大鼠的胰腺。在另一组动物中，将10⁷个DSL-6A/C1细胞直接注射（INJ）到胰腺中。每天监测所有动物直至死亡或观察16周。尸检时，评估原发性肿瘤和腹水的体积、局部和全身肿瘤扩散以及组织学表型。与其他诱导技术相比，IPL-5导致的肿瘤明显更大（12224±1933立方毫米），局部浸润和全身扩散更多（评分：18.3±2.0分），临床肿瘤疾病严重，且有致死性（50%）（IPL-3：283±115立方毫米/3.5±0.8分/0；INJ：752±207立方毫米/4.3±0.8分/8%）。组织学检查显示为中度至高度分化的导管肿瘤，周围有致密的基质。INJ组的腹腔内肿瘤播散与原发性肿瘤生长同时发生，表明注射过程中PaCa细胞发生了扩散。将五个DSL-6A/C1肿瘤碎片原位植入大鼠胰腺为具有免疫活性的啮齿动物提供了一个有效的导管胰腺腺癌临床模型，用于临床前治疗研究。我们使用的播散评分允许对局部和全身肿瘤扩散进行量化。
