CD44highCD24low molecular signature determines the Cancer Stem Cell and EMT phenotype in Oral Squamous Cell Carcinoma

• Revisiting the Cancer Stem Cell markers CD44 and CD24 in OSCC
• Cellular and molecular characterization of CD44highCD24low cells
• CD44highCD24low cells showed EMT property and chemo-resistance.
• Determined gene expression signature of CSC-like cells in oral cancer

Almost all epithelial tumours contain cancer stem-like cells, which possess a unique property of self-renewal and differentiation. In oral cancer, several biomarkers including cell surface molecules have been exploited for the identification of this highly tumorigenic population. Implicit is the role of CD44 in defining CSCs but CD24 is not well-explored. Here we show that CD44highCD24low cells isolated from the oral cancer cell lines, not only express stem cell related genes but also exhibit Epithelial-to-Mesenchymal transition (EMT) characteristics. This CD44highCD24low population gives rise to all other cell types upon differentiation. Typical Cancer Stem Cell (CSC) phenotypes like increased colony formation, sphere forming ability, migration and invasion were also confirmed in CD44highCD24low cells. Drug transporters were found to be over-expressed in CD44highCD24low sub-population thereby contributing to elevated chemo-resistance. To validate our findings in-vivo, we determined the relative expression of CD44 and CD24 in clinical samples of OSCC patients. CD44 expression was consistently high whereas CD24 showed significantly lower expression in tumour tissues. Further, the gene expression profile of the CSC and non-CSC population unravels the molecular pathways which may contribute to stemness. We conclude that CD44highCD24low represents cancer stem-like cells in Oral Squamous Cell Carcinoma.