Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.
Department of Cardiothoracic Surgery, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.
Int J Mol Sci. 2024 May 22;25(11):5619. doi: 10.3390/ijms25115619.
Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.
胰腺导管腺癌（PDAC）的特点是血管生成减少、缺氧和纤维母细胞增生的基质，是人类最致命的恶性肿瘤之一，5 年生存率仅为 7%。胰腺的解剖位置以及疾病早期患者无症状，导致诊断较晚。因此，85%的患者在诊断时表现为不可切除的局部晚期或晚期转移性疾病，依赖于化疗、免疫疗法等替代疗法。这些疗法的反应高度取决于治疗开始时疾病的阶段。因此，在测试新的治疗方法和治疗模式时，在临床前研究中考虑 PDAC 模型的阶段至关重要。我们报告了一种在小鼠中诱导基于细胞的原位胰腺癌模型的标准化方法，并通过超声成像和胰腺星状细胞、成熟成纤维细胞和胶原蛋白水平的组织学分析来鉴定其进展的重要特征。结果表明，在植入研究的 BxPC-3 和 Panc-1 模型后的 5-7 周，早期原发性肿瘤局限于胰腺，并向腹膜浸润进展。晚期表现为广泛生长、腹膜和/或胃壁浸润、转移、成纤维细胞和胶原蛋白水平增加。这些发现可以为未来临床前药物疗效测试的原位胰腺癌模型的定义提供建议。
