GPC5过表达对人肺腺癌A549肿瘤起始细胞生物学功能的影响

目的:探讨磷脂酰肌醇蛋白聚糖-5(glypican 5,GPC5)基因对人肺腺癌A549肿瘤起始细胞(cancer-initiating cells,CICs)生物学功能的影响?方法:采用前期构建的过表达GPC5慢病毒载体稳定转染的细胞株GPC5-A549,无血清培养方法富集A549细胞中的CICs微球,通过定量分析检测微球大小,流式细胞术检测CD133阳性细胞比率,Matrigel和Tanswell小室检测细胞侵袭迁移能力,Western blot检测上皮细胞间质化相关蛋白表达?结果:与对照组相比,过表达GPC5后A549细胞中CICs微球形成数目明显减少,体积变小,CD133阳性率明显下降(P < 0.05);细胞侵袭?迁移能力显著降低(P < 0.05);E-cadherin的蛋白表达明显上调,Vimentin?N-cadherin的表达显著被抑制(P < 0.05)?结论:GPC5过表达能够抑制肺腺癌细胞株A549中CICs的发生?侵袭和迁移,调控上皮细胞间质化相关蛋白表达?

Influence of over-expression of GPC5 on the biological function of human lung adenocaicinoma A549 cancer-initiating cells

Objective: To explore the effects of over-expression of GPC5 on the biological function of human lung adenocarcinoma A549 cancer-initiating cells(CICs). Methods: Lentivims-induced GPC5 over-expression was used for biological functional analyses in human lung adenocarcinoma A549 cell line, including cancer-initiating cell microspherescounting by light microscopy, CD133 positive cells measured by flow cytometry, migration and invasive activity detected by Matrigel and Transwell assay, as well as epithehal-mesenchymal transition-related protein expression detected by Western blot. Results: Compared with the control group, the numbers of cancer-initiating cell microspheres remarkly decreased(P < 0.05) and the percent of CDl33 positive cells was reduced (P < 0.05) in the GPC5 over-expressed group. The over-expression of GPC5 also inhibited the invasion and migration ability of CICs, and led to the down-regulation of Vimentin and N-cadherin, as well as the up-regulation of E-cadherin. Conclusion: The over-expression of GPC5 can inhibit the genesis, invasion and migration of human lung adenocarcinoma A549-CICs, and regulate the expression of EMT related proteins.