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BMC Cancer

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Open Access 01-12-2009 | Research article

Self-renewal and chemotherapy resistance of p75^NTR positive cells in esophageal squamous cell carcinomas

Authors: Sheng-Dong Huang, Yang Yuan, Xiao-Hong Liu, De-Jun Gong, Chen-Guang Bai, Feng Wang, Jun-Hui Luo, Zhi-Yun Xu

Published in: BMC Cancer | Issue 1/2009

Abstract

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, ⁶⁴copper 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 ⁶⁴copper 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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/9/prepub

Title: Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas
Authors: Sheng-Dong Huang
Yang Yuan
Xiao-Hong Liu
De-Jun Gong
Chen-Guang Bai
Feng Wang
Jun-Hui Luo
Zhi-Yun Xu
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-9-9

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