Oral cancer-associated fibroblasts inhibit heat-induced apoptosis in Tca8113 cells through upregulated expression of Bcl-2 through the Mig/CXCR3 axis
Oral cancer-associated fibroblasts inhibit heat-induced apoptosis in Tca8113 cells through upregulated expression of Bcl-2 through the Mig/CXCR3 axis
复制标题
口腔癌相关成纤维细胞通过 Mig/CXCR3 轴上调 Bcl-2 表达，抑制 Tca8113 细胞热诱导的细胞凋亡
DOI：
10.3892/or.2012.2019
复制
发表时间：
2012-12-01
期刊：
影响因子：
4.2
通讯作者：
He, Yongwen
中科院分区：
文献类型：
--
作者：
Bian, Li;Sun, Xin;He, Yongwen
本研究的目的是检测口腔癌相关成纤维细胞分泌的细胞因子及其对热诱导人舌鳞状细胞癌细胞系Tca8113凋亡的调控。我们从人舌鳞状细胞癌和正常口腔黏膜分离了癌相关成纤维细胞(CAF)和正常成纤维细胞(NFs)。用RayBio(R)人细胞因子抗体芯片检测CAF和NFS分泌的细胞因子的表达谱。将CAF或NE细胞培养上清液与新鲜的完整培养液混合制成条件培养液。免疫印迹法检测Tca8113细胞Bax、Bcl2和CXCR3的表达水平。采用碘化丙啶染色结合流式细胞仪检测热诱导Tca8113细胞凋亡率。CAF分泌的趋化因子中的Mig因子的数量明显增加，是正常对照组的19倍。NFS条件培养液对Tca8113细胞Bax/Bcl2表达水平和热诱导凋亡率无明显影响。但在CAF条件培养液中，Bcl2的表达水平显著上调，热诱导的Tca8113细胞的凋亡受到抑制。加入抗Mig或其受体CXCR3的中和抗体后，CAF条件培养液中Bcl2蛋白表达的增强和热诱导Tca8113细胞凋亡的抑制作用明显减弱。CAFS可能通过Mig的旁分泌增加Bcl2的表达，降低Tca8113细胞的热敏感性。
The aim of this study was to detect oral cancer-associated fibroblast-secreted cytokines and their regulation of heat-induced apoptosis in the human tongue squamous cell carcinoma cell line Tca8113. We isolated cancer-associated fibroblasts (CAFs) from human tongue squamous cell carcinoma and normal fibroblasts (NFs) from normal oral mucosa. The expression profiles of cytokines secreted by CAFs and those secreted by NFs were detected using the RayBio (R) human cytokinc antibody microarray. The conditioned medium was prepared by mixing the CAF or NE supernatant cell culture medium with fresh complete medium. The expression levels of Bax, Bcl-2 and CXCR3 in Tca8113 cells were detected by western blot analysis. The heat-induced apoptosis ratio of the Tca8113 cells was detected by propidium iodide staining combined with flow cytometry. The quantity of the Mig factor, one of the chemokines secreted by CAFs, was clearly increased 19-fold when compared with the level in NFs. The conditioned medium of NFs had no obvious effect on the expression levels of Bax/Bcl-2 and the heat-induced apoptosis ratio in the Tca8113 cells. However, the expression levels of Bcl-2 were significantly upregulated and heat-induced Tca8113 cell apoptosis was inhibited in the CA F-conditioned medium. After adding neutralizing antibodies against Mig or its receptor CXCR3, the enhanced expression of the Bcl-2 protein and the inhibited heat-induced apoptosis of Tca8113 cells in the CAF-conditioned medium were significantly attenuated. CAFs may increase the expression levels of Bcl-2 through the paracrine secretion of Mig and reduce the thermosensitivity of Tca8113 cells.