Tsuchikawa Takahiro, Ikeda Hitoshi, Kikuchi Kazunori, Tsuji Takahiro, Baba Tomohisa, Ishizu Akihiro, Tanaka Yuetsu, Kato Hiroyuki, Yoshiki Takashi
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Lab Invest. 2004 Feb;84(2):245-52. doi: 10.1038/labinvest.3700028.
We earlier reported that Fischer 344/jcl strain (F344) rats carrying a unique pX gene of human T lymphocyte virus type I (HTLV-I) under control of a rat lymphocyte-specific protein tyrosine kinase (p56lck) type I promoter (lck-pX rats) spontaneously developed epithelial thymomas from the thymic medulla. To investigate the role of bone marrow cells carrying the HTLV-I pX gene in development of thymomas, the bone marrow of normal F344 rats after lethal irradiation was reconstituted by bone marrow mononuclear cells (BMMC) of lck-pX rats. Epithelial thymomas similar to the original thymoma of lck-pX rats frequently developed in the nontransgenic recipients within 5 months after the BMMC transplantation. The thymomas expressed the pX gene, thereby indicating the thymoma cells to be of donor BMMC origin. Since the thymoma also developed in nontransgenic recipients reconstituted by BMMC depleted of adherent cells, it is suggested that nonadherent BMMC of donor lck-pX rats may migrate to and lodge in the thymus of recipient nontransgenic rats then transform into thymoma cells with epithelial characteristics. The thymoma cells were shown to bind to Ulex europaeus Agglutinin-1 (UEA-1) lectin, which binds epithelial cells in the thymic medulla. It was also shown that the nonadherent BMMC fraction used for bone marrow reconstitution contained a number of UEA-1-positive cells. Taken together, UEA-1 positive BMMC may be progenitor cells of the epithelial thymoma. The epithelial thymoma in lck-pX rats sheds light on epithelial cell development in thymic medulla and for oncogenesis of epithelial thymoma in humans.
我们之前报道过，携带人I型嗜T淋巴细胞病毒（HTLV-I）独特pX基因且该基因受大鼠淋巴细胞特异性蛋白酪氨酸激酶（p56lck）I型启动子控制的Fischer 344/jcl品系（F344）大鼠（lck-pX大鼠）会自发地从胸腺髓质发展出上皮性胸腺瘤。为了研究携带HTLV-I pX基因的骨髓细胞在胸腺瘤发生过程中的作用，对经致死性照射的正常F344大鼠的骨髓，用lck-pX大鼠的骨髓单个核细胞（BMMC）进行了重建。在BMMC移植后5个月内，非转基因受体中经常会出现与lck-pX大鼠原始胸腺瘤相似的上皮性胸腺瘤。这些胸腺瘤表达pX基因，从而表明胸腺瘤细胞来源于供体BMMC。由于在由去除贴壁细胞的BMMC重建的非转基因受体中也出现了胸腺瘤，提示供体lck-pX大鼠的非贴壁BMMC可能迁移并定植于受体非转基因大鼠的胸腺，然后转化为具有上皮特征的胸腺瘤细胞。胸腺瘤细胞显示能与欧洲荆豆凝集素-1（UEA-1）结合，UEA-1可结合胸腺髓质中的上皮细胞。还发现用于骨髓重建的非贴壁BMMC部分含有大量UEA-1阳性细胞。综上所述，UEA-1阳性BMMC可能是上皮性胸腺瘤的祖细胞。lck-pX大鼠中的上皮性胸腺瘤为胸腺髓质上皮细胞的发育以及人类上皮性胸腺瘤的肿瘤发生提供了线索。
