Epigenetic reprogramming and cancer stem cells accumulation in oral carcinoma cell lines resistant to cisplatin.

Cancer stem cells (CSC) are fundamental to increase tumor, and differentiated cells only contribute to tumor bulk. Two hypotheses explain CSC: malignant transformation of stem cells to CSC by mutations; differentiated tumor cells acquire stem properties through dedifferentiation, determined by epigenetic modifications. We assessed two oral carcinoma cell lines resistant to cisplatin (CAL-27 e SCC-9), and isolated cancer stem cells (CSC+) and differentiated cells (CSC-) to investigate differences in aggressiveness and expression of epigenetic genes. Chemoresistant cells presented CSC accumulation. OCT-4, SOX-2 and MMP-9 were accumulated in CSC. CSC+ presented mesenchymal phenotype and CSC- presented epithelial phenotype. Proliferation was activated in CSC+ of CAL-27, and cisplatin increased proliferation of both populations. Clonogenic potential was higher in CSC+. Expression of histone deacetylases was increased and histone acetyltransferases decreased in CSC-. Global expression was higher in CSC- than CSC+. When CSC- were treated with cisplatin, they showed spheres formation. The results suggest that CSC present more aggressive potential, but low epigenetic activity, and epigenetics induces dedifferentiation of CSC-.