Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/γcnull mice:: Suppression by an inhibitor against NF-κB
Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/γcnull mice:: Suppression by an inhibitor against NF-κB
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DOI：
10.1128/jvi.77.9.5286-5294.2003
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发表时间：
2003-05-01
影响因子：
5.4
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Dewan, MZ;Terashima, K;Yamamoto, N
我们利用NOD-SCID/Gammac(空)(NOG)小鼠建立了一种新型的人T细胞白血病病毒1型(HTLV-1)诱发肿瘤的实验模型。该模型对于研究成人T细胞白血病(ATL)/淋巴瘤的肿瘤发生和恶性细胞生长机制是非常有用的，目前尚不清楚。将9株HTLV-1感染细胞株接种于NOG小鼠耳后皮下。早在接种后2-3周，7个细胞系就产生了可见的肿瘤，而两个转化的细胞系未能产生肿瘤。七个品系中有五个产生了一个逐渐生长的大肿瘤，白血病渗透到各种器官中的细胞，最终导致动物死亡。在NOG小鼠中，白血病细胞系形成软性肿瘤，而部分转化细胞系发展为出血性硬性肿瘤。其中一个白血病细胞系ED-40515(-)在2周后不能在具有共同伽马链的NOD-SCID小鼠身上产生可见的肿瘤。在体内，ED-40515(-)细胞株的核因子-kappaB DNA结合活性高于体外培养的细胞，且核因子-kappaB组分发生了变化。BAY 11-7082是一种特异而有效的核因子-kappaB抑制剂，可阻止NOG小鼠原发部位肿瘤生长和白血病在各器官的侵袭。该ATL体内模型可为阐明HTLV-1感染细胞的生长机制以及开发抗ATL新药提供一种新的系统。
We established a novel experimental model for human T-cell leukemia virus type 1(HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.