Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.

Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.
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DOI:
10.1016/j.yexcr.2010.06.013
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发表时间:
2010-10-15
影响因子:
3.7
通讯作者:
Detmar M
Detmar M
中科院分区:
医学3区
文献类型:
--
作者:
Jurisic G;Iolyeva M;Proulx ST;Halin C;Detmar M

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淋巴管系统在炎症和癌症进展中起着重要作用,尽管所涉及的分子机制知之甚少。通过比较离体小鼠肠淋巴管内皮细胞与血管内皮细胞的转录谱研究确定,胸腺细胞抗原1(Thy 1,CD 90)在淋巴管内皮细胞中的表达水平远高于血管内皮细胞。这些发现证实了定量PCR,并在蛋白质水平的流式细胞仪和免疫荧光分析。Thy 1也在肿瘤相关淋巴管中强烈表达,如在小鼠B16黑色素瘤足垫模型中所评估的。阻断Thy 1抑制肿瘤细胞与培养的小鼠淋巴管内皮细胞的粘附。重要的是,用肿瘤坏死因子或佛波醇12-肉豆蔻酸酯13-乙酸酯治疗人真皮微血管内皮细胞导致表达podoplanin的淋巴管内皮细胞中Thy 1上调,但在podoplanin阴性的血管内皮细胞中不上调。此外,人类多形核白细胞和单核白细胞对人类淋巴管内皮细胞的粘附是Thy 1依赖性的。总之,这些结果将Thy 1鉴定为一种新的淋巴管表达基因,并表明其在肿瘤进展和炎症所需的细胞粘附过程中的潜在作用。
The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation.
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