Identification of a subpopulation of chemoresistant cancer cells with adult stem cell properties and embryonic transcription factors in oral squamous cell carcinoma

Background: In South-central Asia, oral cancer ranks among the three most common types of cancer. India alone accounts for 86% of the total oral cancer figures globally. Cancer stem cells (CSCs) are thought to give rise to differentiated tumor cells and to predict tumor recurrence and metastases. This study designed to characterize the CSCs derived from oral squamous cell carcinoma and its identification of correlation with embryonic transcriptional potential. Materials and Methods: Tumor (microscopically ~80% of their areas occupied by tumor cells) and normal counterpart (normal paired noncancerous matched tissue) samples from each histologically confirmed cases of oral squamous cell carcinoma (OSCC) were undertaken in this study. Isolation of stem cells using anti-CD133-positive selection. Expression levels of stem cell surface markers were assessed by flow cytometer. The immunoprofile of these markers was correlated with sex-determining region Y-box 2 (SOX-2), octamer-binding transcription factor 4 (OCT4), and NANOG. The tissue samples of OSCC were studied to identify the localization pattern for CSCs using fluorescence microscopy. Results: Histologically, SOX-2 expression has been identified at all zones exhibiting dysplasia. Isolated CD133+ cells showed differential expression pattern with embryonic transcription factors in tumor cells but not in normal counterpart, which depicts their cancer stemness. Flow cytometry analysis exhibited that SOX-2/OCT4/CD44+with CD133 positive stemness in OSCC malignant tissues was identified to be the best marker for OSCC prediction of the disease. Conclusion: The isolated subpopulation CD133+ cells possess the characteristics of both stem cells and malignant tumors. The findings show that elevated levels of CD133 lead to OSCC invasiveness and metastasis, associated with the upregulation of embryonic and stemness markers. Hence, these tumors may be controlled by restricting the expression of CD133, CD44, OCT4, and SOX2 or by disrupting the molecular pathways that are altered in CSCs.