Jiang Yuhui, Chen Kai, Tang Zhiyu, Zeng Zhu, Yao Weijuan, Sun Dagong, Ka Weibo, He Dongqi, Wen Zongyao, Chien Shu
Department of Biophysics, Health Science Center, Peking University, Beijing, People's Republic of China.
Cell Motil Cytoskeleton. 2006 Aug;63(8):471-82. doi: 10.1002/cm.20138.
TRAIL can selectively induce rapid apoptosis of various types of tumor cells. We induced the expression of TRAIL in Jurkat cells, and measured the adhesion of cells to human umbilical vein endothelial cells (HUVECs) and laminin (LN) in a parallel plate flow chamber system and by using a colorimetric method. The apoptosis percentage, cycle distribution, intracellular Ca(2+) concentration, and adhesion molecule expression of the cells were detected by flow cytometry. Cytoskeleton was observed with a laser confocal microscopy. The roles of adhesion molecules in the cell interaction was defined by their function blocking. The results showed that TRAIL attenuated the adhesion of Jurkat cells to HUVECs and LN, as well as their transendothelial migration. The increased apoptosis and G1-phase cell percentages, decreased intracellular Ca(2+) concentration, depolymerized actin and impaired cell deformability could contribute to the decreased adhesion of Jurkat cells caused by TRAIL. Furthermore, CD11a was found to play a more important role than CD62L in the adhesion of Jurkat cells to HUVECs. These findings contribute to the knowledge on the role of TRAIL in tumor metastasis and provide mechanistic basis for the clinical application of TRAIL and tumor therapy.
肿瘤坏死因子相关凋亡诱导配体(TRAIL)可选择性地诱导各类肿瘤细胞快速凋亡。我们在人急性T淋巴细胞白血病细胞(Jurkat细胞)中诱导TRAIL的表达,并在平行板流动腔系统中通过比色法测定细胞与人脐静脉内皮细胞(HUVECs)及层粘连蛋白(LN)的黏附情况。通过流式细胞术检测细胞的凋亡率、细胞周期分布、细胞内钙离子浓度及黏附分子表达。用激光共聚焦显微镜观察细胞骨架。通过功能阻断来确定黏附分子在细胞相互作用中的作用。结果显示,TRAIL减弱了Jurkat细胞与HUVECs及LN的黏附,以及它们的跨内皮迁移。凋亡增加、G1期细胞百分比升高、细胞内钙离子浓度降低、肌动蛋白解聚及细胞变形能力受损,可能导致TRAIL引起的Jurkat细胞黏附下降。此外,发现CD11a在Jurkat细胞与HUVECs的黏附中比CD62L发挥更重要的作用。这些发现有助于了解TRAIL在肿瘤转移中的作用,并为TRAIL的临床应用和肿瘤治疗提供机制基础。