The role of adhesion molecules, αvβ3, αvβ5 and their ligands in the tumor cell and endothelial cell adhesion
The role of adhesion molecules, αvβ3, αvβ5 and their ligands in the tumor cell and endothelial cell adhesion
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DOI：
10.1097/cej.0b013e3280145c00
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发表时间：
2007-12-01
影响因子：
2.4
通讯作者：
Lou, Jin Ning
中科院分区：
文献类型：
--
作者：
Niu, Ji Xiao;Zhang, Wen Jian;Lou, Jin Ning
肿瘤转移是一个复杂的过程，涉及肿瘤细胞与内皮细胞之间的相互作用，其中一些粘附分子发挥着重要作用。我们的目的是研究粘附分子 alpha v beta 3 和 alpha v beta 5 及其配体发育内皮基因座 1 (Del-1) 和 L1 在体外肿瘤细胞与内皮细胞粘附中的作用。本研究采用实时荧光定量PCR和荧光激活细胞分选仪分析αvβ3、αvβ5和细胞间粘附分子-1在肝窦内皮细胞和肝癌内皮细胞(T3A)上的表达和调控。通过实时 PCR 和蛋白质印迹分析了六种肿瘤细胞系中整合素配体 Del-1 和 L1 的表达和调控。我们发现T3A上αvβ3和αvβ5的表达高于肝窦内皮细胞，而T3A上细胞间粘附分子-1的表达低于肝窦内皮细胞。缺氧24 h后，T3A和肝窦内皮细胞αvβ3和αvβ5表达上调；肝窦内皮细胞细胞间粘附分子-1表达增加，但T3A细胞表达无变化。 Del-1和L1表达水平在不同肿瘤细胞系中存在明显差异，并且在缺氧12小时后受到差异调节。 Del-1和L1表达的肿瘤细胞在T3A中的粘附力高于肝窦内皮细胞，并且在缺氧条件下显着增强。有趣的是，肿瘤细胞粘附可以被αvβ3和αvβ5抗体抑制，但不能被细胞间粘附分子1抗体抑制。不表达Del-1和L1的肿瘤细胞在T3A上的粘附也高于肝窦内皮细胞，但这种粘附不能被αvβ3、αvβ5或细胞间粘附分子1的抗体抑制，表明其他受体也参与其中。综上所述，αvβ3、αvβ5及其配体Del-1、L1在肿瘤细胞从原位迁移的过程中发挥着重要作用。
Tumor metastasis is a complex process involving the interaction between tumor cells and endothelial cells in which some adhesion molecules play an important role. It was our aim to investigate the role of the adhesion molecules, alpha v beta 3 and alpha v beta 5 and their ligands, developmental endothelial locus-1 (Del-1) and L1, in tumor cell adhesion to endothelial cells in vitro. In this study, the expression and regulation of alpha v beta 3, alpha v beta 5 and intercellular adhesion molecule -1 on liver sinusoidal endothelial cells and liver cancer endothelial cells (T3A) were analyzed by real-time PCR and fluorescent-activated cell sorter. The expression and regulation of the integrin ligands, Del-1 and L1, in six tumor cell lines were analyzed by real-time PCR and western blot. We found the expressions of alpha v beta 3 and alpha v beta 5 were higher on T3A than that on liver sinusoidal endothelial cells, whereas expression of intercellular adhesion molecule-1 was lower on T3A than that on liver sinusoidal endothelial cells. After 24 h hypoxia, the expressions of alpha v beta 3 and alpha v beta 5 were upregulated on T3A and liver sinusoidal endothelial cells; the expression of intercellular adhesion molecule-1 was increased on liver sinusoidal endothelial cells, but remained unchanged on T3A. Del-1 and L1 expression levels were obviously diverse in various tumor cell lines and differentially modulated after 12 h hypoxia. The adhesion of tumor cells with Del-1 and L1 expression was higher in T3A than that in liver sinusoidal endothelial cells, and was significantly increased under hypoxic conditions. Interestingly, the tumor cell adherence could be inhibited by antibodies against alpha v beta 3 and alpha v beta 5, but not by an antibody against intercellular adhesion molecule-1. The adhesion of tumor cells without Del-1 and L1 expression was also higher on T3A than that on liver sinusoidal endothelial cells, but the adhesion could not be inhibited by antibodies against alpha v beta 3, alpha v beta 5 or intercellular adhesion molecule-1, suggesting that other receptors are involved. In conclusion, alpha v beta 3, alpha v beta 5 and their ligands Del-1 and L1 play an important role in the process of tumor cells moving from the original place.