基质细胞衍生因子在多发性骨髓瘤细胞迁移和黏附中生物学作用的研究

目的研究基质细胞衍生冈子（SDF-1）存多发性骨髓瘤（MM）细胞迁移、黏附中的生物学作用以及相关信号转导.方法采用流式细胞术检测MM细胞系RPMl8226、XG-1、XG-7细胞黏附分子表达；免疫荧光技术检测SDF-1对细胞形态以及膜表而黏附分子分布的影响；通过微孔隔离实验检测SDF-1对MM细胞的趋化作用及磷脂酰肌醇3激酶（P13K）存趋化过程中的作用；免疫印迹技术检测MM细胞SDF-1对P13K的活化：结果3种MM细胞系不同程度表达多种黏附分子，RPMl8226、XG-7细胞均高表达黏附分子CD29（〉70％）、XG-1、XG-7细胞均高表达CD44（〉80％），XG-7细胞高表达CD49d（〉90％）；3种细胞系CD49e表达水平均较低（〈30％）；这些黏附分子表达水平不能被SDF-1α明显上调。SDF-1α可触发MM细胞的极化形态建立以及诱导CD29、CD49e在细胞膜的重分布。SDF-1α能促进MM细胞对内皮细胞的黏附，并能够诱导MM细胞的迁移，此作用被G蛋白抑制剂PTX及P13K抑制剂wortmannin明显抑制。结论SDF-1α促进MM细胞对内皮细胞的黏附；并触发MM细胞的极化形态建立及诱导黏附分子的重分布，从而通过P13K信号途径诱导MM细胞的迁移。

Study of biological behavior of stromal cell-derived factor-1 on multiple myeloma cell migration and adhesion

Objective To investigate the biological behavior of slromal cell-derived factor-I(SDF-I) on multiple myeloma(MM)cell migration and adhesion and it related signaling pathways.Methods Expres- sion of adhesion molecules on MM cells of RPMI8226,XG-I and XG-7 cells was analysed by flow eytometry, the influence of SDF-1 on CD29 and CD49e distribution by immunofluorescence,the effect of SDF-1 on chem- otaxis of MM cells by lranswell assay.Activation of phosphoinositide-3 kinase(PI3K)in MM cells treated with SDF-1 and by immunoblotting.Results 3 strains of MM cell line expressed many adhesion molecule. RPMI8226,XG-7 cells were all high level of expression of CD29(>70%).XG-I,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 lev- els of expression of CD49e were low(<30%).SDF-I could not upregulate their expression,but eouht trigger the eslablishment of polarized morphology of MM cells and the redistribution of CD29 and CD49e.SDF-1 pro- moted MM cells adhesion to endothelial cells,slimulated 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 wortman- nin.Conclusion SDF-I can promote MM cell adhesion to endothelial cells,trigger establishment of a polar- ized morplmlogy of MM cells and redistribution of adhesion molecules and induce MM cells migration via PI3K signaling pathway.