Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line

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. [Cancer Res 2007;67(8):3716-24]

Smac Mimetics in Combination with TRAIL Selectively Target Cancer Stem Cells in Nasopharyngeal Carcinoma

“…Ã , P < 0.05; ÃÃ , P < 0.01; ÃÃÃ , P < 0.001. (6,9,13,17). Here, we used the SP phenotype to identify CSCs in nasopharyngeal carcinoma and found that S18, a clone of nasopharyngeal carcinoma CNE2 cells, contains high levels of SP cells.…”

“…Although the CSCs represent a small proportion of the tumor cells, they are key players in tumor initiation, recurrence, and metastasis (8)(9)(10)(11)(12). Therefore, CSCs have been considered as an important therapeutic target in anticancer treatments (6,9,(13)(14)(15)(16). Many compounds have been shown to selectively target CSCs in cancers such as salinomycin (6), TbRI inhibitors (9), lupeol (14), sulforaphane (15), thioridazine (16), and others.…”

“…Studies have shown that the side population (SP) cells, identified by having ability to pump out a fluorescent dye (Hoechst 33342), have certain characteristics of CSCs similar to those in liver cancer and gastrointestinal cancer, suggesting that SP phenotype can be a marker of CSC for nasopharyngeal carcinoma (13,17,18). However, no effective compound has been discovered to target nasopharyngeal carcinoma CSCs.…”

B-chronic lymphocytic leukemia chemoresistance involves innate and acquired leukemic side population cells

“…A very minor cell compartment from various tumors [8][9][10][11][12][13] and normal tissues [14][15][16][17] comprises naturally chemoresistant (ABCG2 þ ) cells, with high dye-efflux capacity, that are referred to as 'side population' (SP) cells. 14,18 Although sorting the SP cells usually enriches for a subset displaying stemness features, 8,[9][10][11][12][13]14,18 this phenotype is not only exclusively restricted to stem cells 19 but also shared by some differentiated cells.…”

“…14,18 Although sorting the SP cells usually enriches for a subset displaying stemness features, 8,[9][10][11][12][13]14,18 this phenotype is not only exclusively restricted to stem cells 19 but also shared by some differentiated cells. 20,21 In this study, we tracked chemoresistant subsets of B-CLL cells by the SP technique to clarify the dynamics of chemoresistance in this disease.…”