Abstract
Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family protein and Smoothened protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC.
Highlights
The concept of cancer stem cell (CSC) was introduced many years ago to explain tumor cell heterogeneity, and recent studies suggest that CSC may be responsible for tumorigenesis and contribute to some individuals’ resistance to cancer therapy
After excluding dead cells and cellular debris based on scatter signals and propidium iodide fluorescence, the nasopharyngeal carcinoma (NPC) cell line, CNE-2, was sorted
When preincubated with verapamil for 30 min, the percentage of side population (SP) cells dropped to 0.2% of the total cells (Fig. 1B), which is consistent with reports that Hoechst 33342 exclusion is verapamil sensitive
Summary
The concept of cancer stem cell (CSC) was introduced many years ago to explain tumor cell heterogeneity, and recent studies suggest that CSC may be responsible for tumorigenesis and contribute to some individuals’ resistance to cancer therapy. CSCs are more important than other tumor cells because they are capable of self-renewing, differentiating, and maintaining tumor growth and heterogeneity, playing an important role in both tumorigenesis and therapeutics. Analysis of the hematopoietic system has shown that bone marrow stem cells contain a subpopulation that effluxes the DNA binding dye, Hoechst 33342, out of the cell membrane. These cells are called side population (SP) cells and are shown to have stem cell characteristics and enrich the stem cell population [5,6,7]
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