Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
Exp Cell Res. 2010 Oct 15;316(17):2982-92. doi: 10.1016/j.yexcr.2010.06.013. Epub 2010 Jun 23.
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.
淋巴血管系统在炎症和癌症进展中起着重要作用，尽管其涉及的分子机制尚不清楚。通过对离体培养的小鼠肠淋巴管内皮细胞与血管内皮细胞进行比较转录谱分析，发现胸腺细胞抗原 1（Thy1，CD90）在淋巴管内皮细胞中的表达水平明显高于血管内皮细胞。定量 PCR 及流式细胞术和免疫荧光分析进一步证实了这一发现。在小鼠 B16 黑色素瘤足垫模型中，肿瘤相关淋巴管也强烈表达 Thy1。阻断 Thy1 可抑制肿瘤细胞与培养的小鼠淋巴管内皮细胞的黏附。重要的是，肿瘤坏死因子或佛波醇 12-肉豆蔻酸 13-乙酸酯处理人真皮微血管内皮细胞可导致 podoplanin 表达的淋巴管内皮细胞中 Thy1 的上调，但 podoplanin 阴性的血管内皮细胞则无此变化。此外，人多形核和单核白细胞与淋巴管内皮细胞的黏附依赖于 Thy1。综上所述，这些结果表明 Thy1 是一种新的淋巴管表达基因，并提示其在肿瘤进展和炎症所需的细胞黏附过程中可能发挥作用。
