Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias

  • Mashima Kiyomi
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Azuma Morio
    Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University
  • Fujiwara Ken
    Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University
  • Inagaki Takeshi
    Division of Forensic Medicine, Department of Anatomy, Jichi Medical University
  • Oh Iekuni
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Ikeda Takashi
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Umino Kento
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Nakano Hirofumi
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Morita Kaoru
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Sato Kazuya
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Minakata Daisuke
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Yamasaki Ryoko
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Ashizawa Masahiro
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Yamamoto Chihiro
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Fujiwara Shin-Ichiro
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Hatano Kaoru
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Ohmine Ken
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Muroi Kazuo
    Division of Hematology, Department of Medicine, Jichi Medical University
  • Ohno Nobuhiko
    Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University
  • Kanda Yoshinobu
    Division of Hematology, Department of Medicine, Jichi Medical University

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<p>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.</p>

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