Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias
Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias
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DOI：
10.1267/ahc.19035
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发表时间：
2020-01-01
影响因子：
2.4
通讯作者：
Kanda, Yoshinobu
中科院分区：
文献类型：
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作者：
Mashima, Kiyomi;Azuma, Morio;Kanda, Yoshinobu
白血病是一种难治性造血恶性肿瘤，开发新的治疗药物需要使用荷瘤小鼠模型进行体内研究。虽然在这类研究中通常会检查几个器官来评估病程，但干预措施的有效性和肿瘤细胞在受影响器官中的定位仍不清楚。在这项研究中，我们用两种细胞系（THP-1，人髓单细胞白血病，A20，小鼠B细胞白血病/淋巴瘤）治疗严重免疫缺陷小鼠，产生两种白血病小鼠模型，从组织学上检查了白血病细胞在几个器官中的分布。小鼠的存活取决于肿瘤负荷。虽然移植后21天A20和THP-1肿瘤细胞大量浸润肝脏和脾脏实质，但与THP-1细胞相比，肝脏Glisson包膜结缔组织中几乎没有发现A20细胞。在骨髓中，A20细胞的浸润比THP-1细胞更严重。THP-1和A20细胞在肺中广泛分布，但在小肠中很少观察到。这些发现表明，每种白血病模型在几个受影响的器官中都有独特的肿瘤细胞定位，这可能严重影响疾病的病程和治疗剂的疗效，包括细胞免疫疗法。
Leukemias are refractory hematopoietic malignancies, for which the development of new therapeutic agents requires in vivo studies using tumor-bearing mouse models. Although several organs are commonly examined in such studies to evaluate the disease course, the effectiveness of interventions and the localization of tumor cells in the affected organs are still unclear. In this study, we histologically examined the distribution of leukemia cells in several organs using two leukemic mouse models produced by the administration of two cell lines (THP-1, a human myelomonocytic leukemia, and A20, a mouse B cell leukemia/lymphoma) to severe immunodeficient mice. Survival of the mice depended on the tumor burden. Although A20 and THP-1 tumor cells massively infiltrated the parenchyma of the liver and spleen at 21 days after transplantation, A20 cells were hardly found in connective tissues in Glisson's capsule in the liver as compared with THP-1 cells. In the bone marrow, there was more severe infiltration of A20 cells than THP-1 cells. THP-1 and A20 cells were widely spread in the lungs, but were rarely observed in the small intestine. These findings suggest that each leukemia model has a unique localization of tumor cells in several affected organs, which could critically affect the disease course and the efficacy of therapeutic agents, including cellular immunotherapies.