An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer.
An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer.
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DOI：
10.1097/00006676-200305000-00020
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发表时间：
2003-05-01
期刊：
影响因子：
2.9
通讯作者：
Hines, O Joe
中科院分区：
文献类型：
--
作者：
Hotz, Hubert G;Reber, Howard A;Hines, O Joe
简介：原位的、临床相关的动物模型对于胰腺癌的病理生理学和治疗的研究是必要的。目的：开发一种微创原位肿瘤诱导技术，开发一种量化局部和全身肿瘤扩散的评分系统，并提供一种广泛的高分化至未分化胰腺癌模型。通过无创伤胰腺植入来自皮下供体肿瘤的两个片段或胰腺内注射人肿瘤细胞（MIAPaCa-2、AsPC-1、HPAF-2、Capan-1）在裸鼠中诱导原位肿瘤。动物监测14周或直至死亡。在尸检时评估和分析原发肿瘤体积、局部浸润和全身转移。肉眼观察结果经组织学评价证实。结果：四种细胞系在移植组的肿瘤摄取率均为100%。肿瘤大小、转移扩散和生存率的显著差异取决于分化程度。分化较低的细胞（MIAPaCa-2，AsPC-1）比分化较好的细胞（HPAF-2，Capan-1）引起更高的播散评分和死亡率。临床特征包括恶病质、黄疸和恶性腹水。原位肿瘤细胞注射导致不完全的肿瘤摄取率。此外，早期人工腹部肿瘤扩散被发现在注射动物由于显微镜下细胞损失在injection procedure.CONCLUSIONS：原位移植供体肿瘤片段到裸鼠在技术上是可行的，是上级细胞注射技术。它导致模拟人类疾病的胰腺癌的可再现的局部和全身发展。扩散评分可能有助于在未来的研究中更好地量化治疗效果。
INTRODUCTION: Orthotopic, clinically relevant animal models are necessary for the study of pathophysiology and therapy for pancreatic cancer.AIMS: To develop a minimally traumatic technique of orthotopic tumor induction, to develop a scoring system to quantify local and systemic tumor spread, and to provide a model with a broad range of well-differentiated to undifferentiated pancreatic cancers.METHODOLOGY: Orthotopic tumors were induced in nude mice by atraumatic pancreatic implantation of two fragments from subcutaneous donor tumors or intrapancreatic injection of human tumor cells (MIAPaCa-2, AsPC-1, HPAF-2, Capan-1). Animals were monitored for 14 weeks or until death. Primary tumor volume, local infiltration, and systemic metastasis were assessed and analyzed at autopsy. Macroscopic findings were confirmed by histologic evaluation.RESULTS: Tumor take rate in the implantation group was 100% for all four cell lines. Marked differences with regard to tumor size, metastatic spread, and survival were found depending on the grade of differentiation. Less differentiated cells (MIAPaCa-2, AsPC-1) caused higher dissemination scores and mortality than better-differentiated cells (HPAF-2, Capan-1). Clinical features included cachexia, jaundice, and malignant ascites. Orthotopic tumor cell injection resulted in an incomplete tumor take rate. Moreover, early artificial abdominal tumor spread was found in injected animals due to microscopic cell loss during the injection procedure.CONCLUSIONS: Orthotopic implantation of donor tumor fragments into nude mice is technically feasible and is superior to the cell injection technique. It results in reproducible local and systemic development of pancreatic cancer that mimics the human disease. A dissemination score may help to better quantify therapeutic effects in future studies.