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

¹ State Key Laboratory of Oncology in Southern China and ² Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China and ³ Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China

Requests for reprints: Yi-Xin Zeng, State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510-060, P.R. China. Phone: 86-20-8734-3333; Fax: 86-20-8734-3171; E-mail: zengyix{at}mail.sysu.edu.cn or Shih Hsin Lu, Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100-021, P.R. China, Phone: 86-10-6771-2368; Fax: 86-10-6771-2368; E-mail: shlu{at}public.bta.net.cn.

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]

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