Role of selectins in the tnggenng, growth, and dissemination of T-lymphorna cells:: implication of L-selectin in the growth of thymic lymphorna
Role of selectins in the tnggenng, growth, and dissemination of T-lymphorna cells:: implication of L-selectin in the growth of thymic lymphorna
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DOI：
10.1182/blood-2004-04-1406
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发表时间：
2005-06-15
期刊：
影响因子：
20.3
通讯作者：
St-Pierre, Y
中科院分区：
文献类型：
--
作者：
Bélanger, SD;St-Pierre, Y
我们先前的研究表明，宿主细胞间黏附分子-1(ICAM-1)的表达对淋巴瘤的扩散是必不可少的。由于选择素通常在循环正常细胞的募集中与ICAM-1协同作用，我们研究了它们在淋巴肿瘤发生和转移中的作用。使用选择素缺陷小鼠，我们发现，尽管E-、P-或L-选择素的缺失并不影响辐射诱导的胸腺淋巴瘤的触发，但淋巴瘤细胞上L-选择素的缺失降低了它们在胸腺中的生长能力。然而，通过改变L-选择素介导的胸腺相互作用的完整性，这个缺陷被克服了，就像L选择素缺陷小鼠和过继转移实验所显示的那样。我们还发现，宿主缺乏选择素的表达显著延迟了淋巴瘤向周围组织的扩散。选择素缺陷小鼠对淋巴瘤转移的这种抵抗力依赖于淋巴瘤细胞的内在属性，因为高度致瘤性的变种对缺乏选择素不敏感。观察到淋巴瘤细胞在正常和选择素缺陷小鼠中的传播效率相同，这表明选择素和ICAM-1一样，在转移的后刺阶段发挥影响。这些结果提供了确凿的证据，表明选择素在T细胞淋巴瘤发展的不同阶段发挥着重要作用。(C)2005年，由美国血液病学会提供。
We previously showed that intercellular adhesion molecule-1 (ICAM-1) expression by the host is essential for lymphoma dissemination. Because selectins usually act in a coordinated fashion with ICAM-1 in the recruitment of circulating normal cells, we investigated their implication in lymphomagenesis and metastasis. Using selectin-deficient mice, we found that though the absence of E-, P-, or L-selectins did not affect the triggering of radiation-induced thymic lymphoma, the absence of L-selectin on lymphoma cells reduced their capacity to grow in the thymus. This defect, however, was overcome by altering the integrity of the L-selectin-mediated interactions in the thymus, as shown in L-selectin-deficient mice and by adoptive transfer experiments. We also found that lack of selectin expression by the host significantly delayed the dissemination of lymphomas to peripheral tissues. This resistance of selectin-deficient mice to lymphoma metastasis was dependent on the intrinsic properties of lymphoma cells because highly tumorigenic variants were insensitive to the absence of selectins. Observations that lymphoma cells disseminate with the same efficiency in normal and selectin-deficient mice suggest that selectins exert their influence at the posthorning stage of metastasis, as does ICAM-1. These results provide definitive evidence that selectins play a significant role at different steps of T-cell lymphoma development. (c) 2005 by The American Society of Hematology.