Department of Neuroscience and Pharmacology, University of Iowa, 2-570 Bowen Science Building, 51 Newton Road, Iowa City, IA, 52242, USA.
Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, USA.
Sci Rep. 2021 May 13;11(1):10252. doi: 10.1038/s41598-021-89866-1.
Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients present with metastatic liver tumors at diagnosis and current therapies fail to improve overall survival. Pre-clinical models of pNEN metastasis are needed to advance our understanding of the mechanisms driving the metastatic process and for the development of novel, targeted therapeutic interventions. To model metastatic dissemination of tumor cells, human pNEN cell lines (BON1 and Qgp1) stably expressing firefly luciferase (luc) were generated and introduced into NSG immunodeficient mice by intracardiac (IC) or intravenous (IV) injection. The efficiency, kinetics and distribution of tumor growth was evaluated weekly by non-invasive bioluminescent imaging (BLI). Tumors formed in all animals in both the IC and IV models. Bioluminescent Qgp1.luc cells preferentially metastasized to the liver regardless of delivery route, mimicking the predominant site of pNEN metastasis in patients. By comparison, BON1.luc cells most commonly formed lung tumors following either IV or IC administration and colonized a wider variety of tissues than Qgp1.luc cells. These models provide a unique platform for testing candidate metastasis genes and anti-metastatic therapies for pNENs.
胰腺神经内分泌肿瘤（pNENs）是一种生长缓慢、发病率不断上升的癌症，一旦发生转移，目前缺乏有效的治疗方法。不幸的是，近一半的 pNEN 患者在诊断时已出现肝转移瘤，而目前的治疗方法并不能改善总体生存率。需要建立 pNEN 转移的临床前模型，以深入了解驱动转移过程的机制，并开发新的、有针对性的治疗干预措施。为了模拟肿瘤细胞的转移扩散，我们构建了稳定表达萤火虫荧光素酶（luc）的人 pNEN 细胞系（BON1 和 Qgp1），并通过心内（IC）或静脉（IV）注射将其导入 NSG 免疫缺陷小鼠体内。每周通过非侵入性生物发光成像（BLI）评估肿瘤生长的效率、动力学和分布。在 IC 和 IV 模型中，所有动物均形成了肿瘤。无论给药途径如何，生物发光的 Qgp1.luc 细胞均优先转移到肝脏，模拟了患者中 pNEN 转移的主要部位。相比之下，BON1.luc 细胞在 IV 或 IC 给药后最常形成肺肿瘤，并比 Qgp1.luc 细胞定植更广泛的组织。这些模型为测试候选转移基因和针对 pNENs 的抗转移治疗提供了独特的平台。
