Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.
Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.
复制标题
α4-整合素在淋巴瘤转移的不同步骤中的主要作用。
DOI：
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发表时间：
1996
影响因子：
11.1
通讯作者：
B. Holzmann
中科院分区：
文献类型：
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作者：
U. Gosslar;P. Jonas;A. Luz;A. Lifka;D. Naor;A. Hamann;B. Holzmann
为了分析α4整合素在淋巴瘤转移中的作用，通过逆转录病毒介导的基因转移获得了不同于α4整合素表达的T细胞淋巴瘤LB亚系。利用LBAlpha4细胞和对照LBNTK细胞，我们证明了Alpha4整合素的表达强烈地抑制了Lb淋巴瘤细胞在静脉注射后在次级淋巴器官如脾、肠系膜和外周淋巴结或Peyer‘s结中的转移形成。注射同基因BALB/c小鼠。此外，α4整合素的表达抑制了肝、肺和肾转移瘤的发展。淋巴细胞在骨髓中的扩增不受α4整合素表达的影响。用~(51)Cr标记的淋巴瘤细胞进行体内迁移实验表明，低转移的LB-α4细胞在所有被检测的靶器官中以与高转移的LB-NTK细胞相同的效率蓄积，甚至在粘膜淋巴器官中也有浓集。总而言之，这些结果表明，α4整合素在靶器官入侵后的一个阶段抑制淋巴瘤细胞的转移形成。
To analyze the role of alpha4-integrins in lymphoma metastasis, sublines of the T-cell lymphoma LB were generated by retrovirus-mediated gene transfer that differ exclusively in the expression of alpha4-integrins. Using LB-alpha4 and control LB-NTK cells, we demonstrate that expression of alpha4-integrins strongly suppresses metastasis formation of LB lymphoma cells in secondary lymphoid organs such as spleen, mesenteric and peripheral lymph nodes, or Peyer's patches after i.v. injection into syngeneic BALB/c mice. Moreover, alpha4-integrin expression inhibited development of metastatic tumors in liver, lung, and kidney. Expansion of LB lymphoma cells in bone marrow was not affected by alpha4-integrin expression. In vivo migration assays using 51Cr-labeled lymphoma cells demonstrated that low-metastatic LB-alpha4 cells accumulated with the same efficiency as high-metastatic LB-NTK cells in all target organs examined and were even enriched in mucosal lymphoid organs. Collectively, these results indicate that alpha4-integrins inhibit metastasis formation of lymphoma cells at a stage subsequent to the invasion of target organs.