title: Oral cancer-associated fibroblasts inhibit heat-induced apoptosis in             Tca8113 cells through upregulated expression of Bcl-2 through the Mig/CXCR3 axis.
abstract: 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® human cytokine antibody microarray. The             conditioned medium was prepared by mixing the CAF or NF 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 CAF-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.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Kewei
authors.initials: K
authors.lastname: Jin
authors.forename: Yongwen
authors.initials: Y
authors.lastname: He
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D049109:Cell Proliferation; D054370:Chemokine CXCL9 / Q000378:metabolism; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D017077:Culture Media, Conditioned; D019253:Proto-Oncogene Proteins c-bcl-2; D054367:Receptors, CXCR3