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Cancer stem-like cells enriched with CD29 and CD44 markers exhibit molecular characteristics with epithelial–mesenchymal transition in squamous cell carcinoma

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An Erratum to this article was published on 07 April 2017

Abstract

Increasing evidences have indicated that only a phenotypic subset of cancer cells, termed as the cancer stem cells (CSCs), is capable of initiating tumor growth and provide a reservoir of cells that cause tumor recurrence after therapy. Epithelial–mesenchymal transition (EMT), a cell type change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, plays a critical role not only in tumor metastasis but also in tumor recurrence and contributes to drug resistance. Accumulating evidence has shown that cells with an EMT phenotype are rich sources for CSCs, suggesting a biological link between EMT and CSCs; thus study on the link will help understand the cellular and molecular mechanisms of tumor metastasis and drug resistance. CD29 is involved in EMT through cross-talk with cadherins and CD44 has been reported as a successful used marker for CSCs. Here, we try to address whether combination of CD29 and CD44 could be used to identify cancer stem-like cells undergoing EMT in squamous cell carcinoma (SCC) and compare the molecular differences between CD29high/CD44high and CD29low/CD44low cells in SCC. Expression pattern of CD29 and CD44 was analyzed in tissues of skin SCC and cultured A431 cells by immunostaining. Subtype cells of CD29high/CD44high and CD29low/CD44low A431 were sorted by fluorescence-activated cell sorting and proliferating abilities were assayed by cell counting, colony forming and tumorigenicity in NOD/SCID mice. Finally, to probe more deeply into the molecular differences between CD29high/CD44high and CD29low/CD44low A431 cells, gene microarray analysis was applied to compare gene expression profiling. Staining of CD29 and CD44 showed similar heterogeneous expression pattern with positive cells located in the invasion front of SCC tissue as well as in cultured A431 cells. Sorted CD29high/CD44high A431 cells had higher proliferating ability in vitro and in NOD/SCID mice as compared with CD29low/CD44low cells. Gene profiling identified differentiated gene expressions between CD29high/CD44high and CD29low/CD44low A431 cells. These genes are involved in cell cycle, cell malignant transformation, metastasis, drug resistance and EMT, implying that CD29high/CD44high cells have properties of CSCs and EMT. Our present results demonstrated heterogeneous gene expression patterns and different biological behavior in SCC. Combination of CD29 and CD44 can be used as markers to enrich CSCs in human SCC. Moreover, CD29high/CD44high cells exhibit molecular characteristics of EMT, suggesting that CSC-associated pathways were involved in EMT. Studies on correlation of CSCs and the cells undergoing EMT may explain some aspects of tumor progression and drug resistance.

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Acknowledgments

We are grateful to Dr Zhishang Hu, Dr. Chunchun Liu, especially to Prof. Haiying Hang (from Institute of Biophysics, Chinese Academy of Sciences) who provided us with great advice and technical supports. We appreciate help from Prof. Zhi Liu (from North Carolina University, USA) for critically reading the manuscript and for comments. We thank Dr. Jiahe Zhang (First hospital, Xi’an, China) for statistics analysis. This work was supported by National Natural Science Funds of China (No. 81171490), Program for New Century Excellent Talents in University (NCET- NCET-93YXDW11000016), Program for Changjiang Scholars and Innovative Research Team in University PCSIRT:1171), Funds of Xi’an Jiaotong University 08143023 and Funds of Northwest Hospital of Xi’an Jiaotong University RC(XM)200904.

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  1. Department of Dermatology, Northwest Hospital, Xi’an Jiaotong University, Xi’an, 710004, China

    Songmei Geng, Yuanyuan Guo, Qianqian Wang & Lan Li

  2. Department of Hematology, Northwest Hospital, Xi’an Jiaotong University, Xi’an, 710004, China

    Jianli Wang

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  1. Songmei Geng
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Correspondence to Songmei Geng.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00403-017-1737-0.

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Geng, S., Guo, Y., Wang, Q. et al. Cancer stem-like cells enriched with CD29 and CD44 markers exhibit molecular characteristics with epithelial–mesenchymal transition in squamous cell carcinoma. Arch Dermatol Res 305, 35–47 (2013). https://doi.org/10.1007/s00403-012-1260-2

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