Saalbach A, Hildebrandt G, Haustein U-F, Anderegg U
Department of Dermatology, University of Leipzig, 04103 Leipzig, Germany.
Microvasc Res. 2002 Jul;64(1):86-93. doi: 10.1006/mvre.2002.2401.
The expression of adhesion molecules on endothelial cells as well on tumor cells regulates and directs adhesion and transmigration of tumor cells through the endothelial cell barrier as one prerequisite to the formation of metastasis. Thy-1 is an inducible activation-associated cell-adhesion molecule on human dermal microvascular endothelial cells (HDMECs). In this study we investigated whether the Thy-1/Thy-1 ligand interaction may also play a role in adhesion of melanoma cells to endothelial cells. In situ, a strong Thy-1 expression on endothelial cells in melanoma and melanoma metastases was observed. In vitro, Thy-1 expression was stimulated by melanoma-cell-derived soluble factors, reflecting that Thy-1 expression in melanoma is not only due to a nonspecific inflammatory response. TNFalpha and bFGF were not responsible for this effect. In vitro and in situ a Thy-1 ligand was detected on melanoma cells. In cell-adhesion assays we showed the involvement of the Thy-1/Thy-1 ligand interaction in adhesion of melanoma cells to HDMECs. In summary, the data support that the study of the Thy-1/Thy-1 ligand interaction might give a more detailed insight into the regulation and direction of adhesion of melanoma cells to endothelial cells as one critical step in the formation of tumor metastasis.
内皮细胞以及肿瘤细胞上黏附分子的表达,作为肿瘤转移形成的一个先决条件,调节并引导肿瘤细胞通过内皮细胞屏障的黏附和迁移。Thy-1是人类真皮微血管内皮细胞(HDMECs)上一种可诱导的与激活相关的细胞黏附分子。在本研究中,我们调查了Thy-1/Thy-1配体相互作用是否也在黑色素瘤细胞与内皮细胞的黏附中发挥作用。在原位,观察到黑色素瘤及黑色素瘤转移灶中的内皮细胞有强烈的Thy-1表达。在体外,黑色素瘤细胞衍生的可溶性因子刺激了Thy-1的表达,这表明黑色素瘤中Thy-1的表达不仅是由于非特异性炎症反应。肿瘤坏死因子α和碱性成纤维细胞生长因子对此效应无作用。在体外和原位均在黑色素瘤细胞上检测到Thy-1配体。在细胞黏附试验中,我们表明Thy-1/Thy-1配体相互作用参与了黑色素瘤细胞与HDMECs的黏附。总之,数据支持对Thy-1/Thy-1配体相互作用的研究可能会更详细地深入了解黑色素瘤细胞与内皮细胞黏附的调节和导向,这是肿瘤转移形成中的关键步骤。