Zhang Xiao-hui, Fu Jin-xiang, Zhang Jian-hua, Zhang Yang-min
Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhonghua Xue Ye Xue Za Zhi. 2006 Apr;27(4):240-3.
To investigate the biological behavior of stromal cell-derived factor-1 (SDF-1) on multiple myeloma (MM) cell migration and adhesion and it related signaling pathways.
Expression of adhesion molecules on MM cells of RPMI8226, XG-1 and XG-7 cells was analysed by flow cytometry, the influence of SDF-1 on CD29 and CD49e distribution by immunofluorescence, the effect of SDF-1 on chemotaxis of MM cells by transwell assay. Activation of phosphoinositide-3 kinase (PI3K) in MM cells treated with SDF-1 and by immunoblotting.
3 strains of MM cell line expressed many adhesion molecule. RPMI8226, XG-7 cells were all high level of expression of CD29 (> 70%). XG-1, XG-7 cells were all high level of expression of CD44 (> 80%), and XG-7 cells was of CD49d (> 90%). In all of 3 strains, the levels of expression of CD49e were low (< 30%). SDF-1 could not upregulate their expression, but could trigger the establishment of polarized morphology of MM cells and the redistribution of CD29 and CD49e. SDF-1 promoted MM cells adhesion to endothelial cells, stimulated phosphorylation of P85 subunit of PI3K in MM cells and induced MM cells migration, which were inhibited by G protein inhibitor PTX and PI3K inhibitor wortmannin.
SDF-1 can promote MM cell adhesion to endothelial cells, trigger establishment of a polarized morphology of MM cells and redistribution of adhesion molecules and induce MM cells migration via PI3K signaling pathway.
探讨基质细胞衍生因子-1(SDF-1)对多发性骨髓瘤(MM)细胞迁移和黏附的生物学行为及其相关信号通路。
采用流式细胞术分析RPMI8226、XG-1和XG-7细胞株MM细胞上黏附分子的表达,免疫荧光法检测SDF-1对CD29和CD49e分布的影响,Transwell法检测SDF-1对MM细胞趋化性的影响。用免疫印迹法检测SDF-1处理的MM细胞中磷酸肌醇-3激酶(PI3K)的激活情况。
3株MM细胞系均表达多种黏附分子。RPMI8226、XG-7细胞CD29表达均为高水平(>70%)。XG-1、XG-7细胞CD44表达均为高水平(>80%),XG-7细胞CD49d表达为高水平(>90%)。3株细胞中CD49e表达水平均较低(<30%)。SDF-1不能上调其表达,但可引发MM细胞极化形态的形成及CD29和CD49e的重新分布。SDF-1促进MM细胞与内皮细胞黏附,刺激MM细胞中PI3K的P85亚基磷酸化并诱导MM细胞迁移,G蛋白抑制剂PTX和PI3K抑制剂渥曼青霉素可抑制上述作用。
SDF-1可促进MM细胞与内皮细胞黏附,引发MM细胞极化形态的形成及黏附分子的重新分布,并通过PI3K信号通路诱导MM细胞迁移。