Studies on the mechanism of cell growth of ATL cells

ATL细胞生长机制的研究

• 批准号: 06404040
• 负责人: UCHIYAMA Takashi
• 金额: $ 16.9万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06404040/
• 关键词: ATL; HTLV-I; Tumorigenicity; SCID mouse; IL-2; Adhesion molecule; OX40; gp34

Summary of our studies on the mechanism of neoplastic cell growth in vivo of ATL cells are as follows. 1.We established a model of in vivo cell proliferation of ATL cells using SCID mice. 2.Fresh leukemic cells from ATL patients and HTLV-I-infected cell lines derived from leukemic cell clones showed tumorigenicity. HTLV-I-infected cell lines of nonleukemic cell origin and tax-transfected in vitro immortalized cells did not show tumorigenicity. 3.It appears that HTLV-I-expression is not needed for the cell growth of ATL cells in vivo and IL-2 autocrine mechanism in not involved in the cell growth in vivo. 4.We demonstrated the organ infiltration pattern of ATL cells in vivo using the radiolabeled anti-Tac antibody as a tracer. 5.We developed two monoclonal antibodies (MoAb) which block the unknown adhesion pathway between ATL cells and human umbilical vein endothelial cells (HUVEC). After characterizing the antigen, we succeeded in the cloning of its cDNA.The Agrecognized by the MoAb was found to be human OX40 homologue, a member of TNF receptor family. We then, for the first time, demonstrated that OX40 and its ligand (gp34) directly mediated the adhesion between ATL cells and HUVEC.Furthermore, we demonstrated the expression of gp34 on other vascular endothelial cells. OX40/gp34 may play a key role not only in the neoplastic cell growth and organ infiltration of ATL cells but also in the interaction between activated T cells and vascular endothelial cells which leads to infalmmatory lesions.

我们对ATL细胞体内肿瘤细胞生长机制的研究总结如下。1.建立了ATL细胞在SCID小鼠体内增殖的模型。2.来自ATL患者的新鲜白血病细胞和来自白血病细胞克隆的HTLV-I感染的细胞系显示出致瘤性。非白血病细胞来源的HTLV-I感染细胞系和紫杉醇转染的体外永生化细胞未显示致瘤性。3.ATL细胞在体内的生长不需要HTLV-1的表达，IL-2的自分泌机制不参与ATL细胞的体内生长。4.用放射性标记的抗Tac抗体作为示踪剂，在体内观察了ATL细胞的器官浸润模式。5.我们研制了两种单克隆抗体（MoAb），它们阻断了ATL细胞与人脐静脉内皮细胞（HUVEC）之间的未知粘附途径。经鉴定，成功克隆了该抗原的cDNA，其识别的抗原为TNF受体家族成员之一的人OX 40同源物。我们首次证实了OX 40及其配体（gp 34）直接介导ATL细胞与HUVEC的粘附，并证实了gp 34在其他血管内皮细胞上的表达。OX 40/gp 34不仅在ATL细胞的肿瘤细胞生长和器官浸润中起关键作用，而且在活化的T细胞和血管内皮细胞之间的相互作用中起关键作用，从而导致炎症性病变。

项目成果

Takashi Uchiyama et al.: "Pathophysiology of adult T cell leukemia cells-cell glowth characteristics-" Adult T cell leukemia(ed.by K.Takatsuki). 181-203 (1994)

Takashi Uchiyama 等人：“成人 T 细胞白血病细胞的病理生理学 - 细胞发光特征 -” 成人 T 细胞白血病（K.Takatsuki 编辑）。

Uchiyama T.: "Pathophysiology of adult T cell leukemia cells : cell growth characteristics" "Adult T cell leukemia" oxford University Press. 181-203 (1994)

Uchiyama T.：“成人T细胞白血病细胞的病理生理学：细胞生长特征”“成人T细胞白血病”牛津大学出版社。

Akifuji Takaori-Kondo et al.: "Detection of homing,proliferation and iufiltration sites of adult T cell leukemia cells in severe combined immunodetiaency mice using radio." Jpn.J.Concer Res.(in press). (1995)

Akifuji Takaori-Kondo 等人：“使用无线电检测严重联合免疫缺陷小鼠中成人 T 细胞白血病细胞的归巢、增殖和渗透位点。”

Imada K.: "Tumorigenicity of HTLV-I infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo" Blood. 86. 2350-2357 (1995)

Imada K.：“HTLV-I 感染细胞系在严重联合免疫缺陷小鼠中的致瘤性以及体内细胞增殖的特征”血液。

Hosono M.: "Radiommunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice" Nuclear Medicine and Biology. 22. 869-874 (1995)

Hosono M.：“在严重联合免疫缺陷小鼠中使用抗白细胞介素 2 受体抗体对人类白血病进行放射免疫检测”核医学和生物学。