中国肿瘤生物治疗杂志2018,Vol.25Issue(4):357-362,6.DOI:10.3872/j.issn.1007-385x.2018.04.007
TGF-β2通过基质金属蛋白酶通路影响胶质瘤干细胞的侵袭能力
TGF-β2 enhances invasion ability of glioma stem cell through matrix metalloproteinase pathway
摘要
Abstract
Objective:To study the effect and possible mechanism of TGF-β2 on the invasion of glioma stem cells (GSCs).Methods:Tumor tissues of 8 patients with glioblastoma multiforme,who underwent resection at Department of Neurosurgery of the First Affiliated Hospital of China Medical University during April 2016 to April 2017,were collected.The primary culture of glioma cells were conducted with trypsin digestion.Partial primary glioma cells were seeded into serum-free DMEM/F12 culture medium containing EGF,bFGF and B27 to obtain suspension of tumor spheres.Immunoflurenscent staining and differentiation assay were used to detect whether the tumor spheres were GSCs.TGF-β2 secretion ability of GSCs was determined by ELISA assay.After transfection of TGF-β2 siRNA,the invasion ability of glioma stem cells was determined by Transwell assay.Western blotting was used to examine the effect of TGF-β2 on expression of matrix metalloproteinases (MMP) in glioma stem cells.Results:The suspended tumor spheres were proved to be GSCs by immunofluorescent staining and differentiation assay;the tumor spheres expressed the marker of GSCs (CD133)and had the ability to multi-differentiate (glia and neuronal cells).Compared with the primary glioma cells,Glioma stem cells exerted significantly improved TGF-β2 secretion ability ([74.13±3.63] vs [46.13±2.61] pg/ml,P<0.05);and TGF-β2 silencing significantly reduced the invasion ability of glioma stem cells ([105.71 ±8.69] vs [63.67±5.93],P<0.05) and inhibited MMP-2 and MMP-9 expressions.Conclusion:TGF-β2 can promote the invasiveness of glioma stem cells through MMP-2 and MMP-9 pathway.关键词
胶质瘤干细胞/转化生长因子-β2/基质金属蛋白酶/侵袭Key words
glioma stem cell/TGF-β2/matrix metalloproteinase/invasion分类
医药卫生引用本文复制引用
张东勇,王一维,张路阳,王维,刘强,李振航,王运杰,仇波..TGF-β2通过基质金属蛋白酶通路影响胶质瘤干细胞的侵袭能力[J].中国肿瘤生物治疗杂志,2018,25(4):357-362,6.基金项目
辽宁省博士启动基金资助项目(No.201501004).Project supported by the Doctoral Startup Foundation of Liaoning Province (No.201501004) (No.201501004)