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Background  p75 NTR  has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75 NTR  in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75 NTR+  cells.    Methods  p75 NTR  expression in ESCC was assessed by immunohistochemistry. p75 NTR+  and p75 NTR-  cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75 NTR+  and p75 NTR-  cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay,  64 copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75 NTR+  cells.    Results  In ESCC specimens, p75 NTR  was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75 NTR+  cells was 1.6%–3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75 NTR+  cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75 NTR+  cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75 NTR+  cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, β1-integrin and β4-integrin, were lower in p75 NTR+  cells. In addition, p75 NTR+  cells generated both p75 NTR+  and p75 NTR-  cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75 NTR+  cells were found to be more resistant to DDP and exhibited lower  64 copper accumulation than p75 NTR-  cells.    Conclusion  Our results demonstrated that p75 NTR+  cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75 NTR+  cells may probably be attributable to decreased expression of CTR1.

Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas