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The aim of this study was to detect oral cancer-associated fibroblast-secretedcytokines and their regulation of heat-induced apoptosis in the human tongue squamouscell carcinoma cell line Tca8113. We isolated cancer-associated fibroblasts (CAFs)from human tongue squamous cell carcinoma and normal fibroblasts (NFs) from normaloral mucosa. The expression profiles of cytokines secreted by CAFs and those secretedby NFs were detected using the RayBio® human cytokine antibody microarray. Theconditioned medium was prepared by mixing the CAF or NF supernatant cell culturemedium with fresh complete medium. The expression levels of Bax, Bcl-2 and CXCR3in Tca8113 cells were detected by western blot analysis. The heat-induced apoptosisratio of the Tca8113 cells was detected by propidium iodide staining combinedwith flow cytometry. The quantity of the Mig factor, one of the chemokines secretedby CAFs, was clearly increased 19-fold when compared with the level in NFs. Theconditioned medium of NFs had no obvious effect on the expression levels of Bax/Bcl-2and the heat-induced apoptosis ratio in the Tca8113 cells. However, the expressionlevels of Bcl-2 were significantly upregulated and heat-induced Tca8113 cell apoptosiswas inhibited in the CAF-conditioned medium. After adding neutralizing antibodiesagainst Mig or its receptor CXCR3, the enhanced expression of the Bcl-2 proteinand the inhibited heat-induced apoptosis of Tca8113 cells in the CAF-conditionedmedium were significantly attenuated. CAFs may increase the expression levelsof Bcl-2 through the paracrine secretion of Mig and reduce the thermosensitivityof Tca8113 cells.

Oral cancer-associated fibroblasts inhibit heat-induced apoptosis in Tca8113 cells through upregulated expression of Bcl-2 through the Mig/CXCR3 axis