CD133 Positive Head and Neck Squamous Cell Carcinoma Exhibit Invasive Properties after Exposure to Low Concentrations of Chemotherapy Reagents

In the treatment of patients with head and neck squamous cell carcinoma (HNSCC), the efficacy of intravenous chemotherapy is often unreliabledue to the variable growth of vasculature in such lesions. As such, chemotherapy reagents are often unable to reach lesions at an effective concentration required to kill cancer cells. Recent reports have shown that the bulk of cancer cells have subpopulations with stem cells that have characteristics enabling drug resistance, high migration activity and invasive capabilities. These cancer cells express CD133 and have been suggested to be present in HNSCC. Therefore, we investigated whether low concentrations of chemotherapy reagents might influence the biological behavior of cancer cells, particularly CD133+ HNSCC cells. In this study, we successfully isolated CD133+ cancer cells from HNSCC cell lines and showed that CD133+ HNSCC cells exhibited higher invasive activity after exposure to low concentrations of chemotherapy reagents. Immunofluorescent and quantitative real-time PCR demonstrated that CD133+ cells undergo epithelial-mesenchymal transition (EMT), with a higher expression of mesenchymal markers compared to parental cells. We concluded that CD133+ cells in HNSCC would not only survive in the presence of low concentrations of chemotherapy reagents but also increase capacity for migration and invasion via EMT. In clinical practice, select HNSCC patients with comorbidities may receive a reduced dose of chemotherapy to reduce side effects. However, our findings indicate that a reduction in dose could in fact lead to treatment failure due to activation of EMT mechanisms particularly in CD133+ cancer cells.

Keywords: Head and neck squamous cell carcinoma, cancer stem cells, CD133, chemotherapy reagents, epithelial-mesenchymal transition.