Stem cell profiling in head and neck cancer reveals an Oct-4 expressing subpopulation with properties of chemoresistance

Objectives: In the past decade cancer, including head and neck squamous cell cancer (HNSCC), is increasingly being regarded as a stem cell associated disease which arises from cells with the property of stemness. According to the cancer stem cell (CSC) theory, only a specific subpopulation of cancer cells has the ability to initiate and perpetuate cancer growth, especially under treatment. In this article we describe a subpopulation of cells within HNSCC that expresses the stemness factor Oct-4, which leads to apoptotic resistance after exposure to chemotherapeutic agents. Materials and methods: Permanent cell lines and HNSCC tissue were analyzed for expression of stem cell markers using flow cytometric, immunohistochemical approaches and an antibody based protein array. Chemotherapeutic agent-induced growth inhibition, also known as "enrichment", was determined by the colorimetric cell proliferation assay (MTT-based) and putative stem cell markers were investigated by flow cytometry. Results: Various potential CSC markers were identified in heterogenic expression profiles in permanent cell lines and solid tumors. Our data suggest the Oct-4A isoform as a marker of stemness in HNSCC and the enrichment of cancer stem-like cells by various chemotherapeutic agents was associated with a significantly higher expression of Oct-4. Conclusion: This data suggests that many potential CSC markers are expressed on different expression levels in HNSCC. Among these markers Oct-4(A) plays a pivotal role in the detection of cancer cells with enhanced chemoresistance and provide evidence for the existence of cancer stem-like cells in HNSCC.