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