Cancer stemness of CD10-positive cells regulated by Hedgehog pathway promotes the resistance to cisplatin in oral squamous cell carcinoma

Abstract

Objective: To explore the role of CD10 in cisplatin resistance of oral squamous cell carcinoma (OSCC) and its association with the Hedgehog (Hh) signaling pathway and cancer stem cells (CSCs).

Methods: The correlation between cell viability and CD10 expression was analyzed in different OSCC cell lines after the cisplatin treatment. Genes related to chemotherapy resistance, cancer stem cells and the epithelial-mesenchymal transition were detected by quantitative real-time PCR (qPCR) in CD10^high and CD10^low OSCC cells. Mouse xenograft model and venous metastasis model were used to explore the potential regulatory mechanism of the resistance effect of CD10 on cisplatin.

Results: The higher expression of CD10 gene in different cell lines displayed enhanced cisplatin resistance ability. The expression of genes related to chemotherapy resistance, cell stemness, and the epithelial-mesenchymal transition was significantly higher in CD10^high cells compared with CD10^low cells. Moreover, the combination of cisplatin and Hh pathway inhibitors significantly reduced the resistance of CD10 to cisplatin in the xenograft model and venous metastasis models.

Conclusion: CD10-positive cells are implicated in developing cisplatin resistance of OSCC, which could be related to its cancer stem cell characteristics regulated by the Hedgehog pathway.

Keywords: CD10; Hedgehog pathway; cancer stem cell; chemotherapy resistance; oral squamous cell carcinoma.