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Journal of Cancer Research and Clinical Oncology

, Volume 143, Issue 9, pp 1687–1699 | Cite as

Human circulating and tissue gastric cancer stem cells display distinct epithelial–mesenchymal features and behaviors

  • Shengliang Zhang
  • Yanna Shang
  • Tie Chen
  • Xin Zhou
  • Wengtong Meng
  • Chuanwen Fan
  • Ran Lu
  • Qiaorong Huang
  • Xue Li
  • Xu Hong
  • Zongguang Zhou
  • Jiankun HuEmail author
  • Xianming Mo
Original Article – Cancer Research

Abstract

Introduction

Metastasis is a leading cause of cancer-related-deaths worldwide. Recently, cancer stem cells (CSCs) have been believed to be responsible for tumor initiation and metastasis, but till now, difference of cellular features and behaviors between CSCs from tumor tissues (TCSCs) and circulation (CCSCs) remains largely unknown, which hinders the progression of targeted therapies for metastasis.

Methods and Results

Here, we provide the features of circulating gastric cancer stem cells (CGCSCs) isolated from human gastric adenocarcinoma. The CGCSCs and TGCSCs were culture in a same serum free stem cell culture medium, however the morphology are different with each other. EMT-associated markers were measured by Immunofluorescence, Western Blotting, and RT-PCR methods, and the results indicated that the CGCSCs and TGCSCs carry different epithelial–mesenchymal features. And then, proliferation and apoptosis assays revealed that the CGCSCs exhibited characteristics of higher proliferation and resistance to apoptosis in vitro. Soft agar assay and nude mice tumorigenicity assay displayed strong tumorigenicity of CGCSCs. Finally, Matrigel invasion assays and in vivo experimental metastasis assay were also performed, which demonstrated that CGCSCs carry high invasive and metastatic capabilities than TGCSCs.

Conclusions

As expected, the CGCSCs indeed showed extremely invasive and metastatic properties. They also exhibited distinctive mesenchymal phenotypes, high self-renewal, proliferative capabilities, tumor induction and low apoptosis. Interestingly, CGCSCs show small cell-size than TGCSCs (tissue gastric cancer stem cells). The findings might help us to understand the biological characteristic of CGCSCs deeply, and give light to strategies for cancer therapies.

Keywords

Metastasis Cancer stem cells Mesenchymal Self-renewal Proliferative capabilities Apoptosis 

Notes

Acknowledgements

The relevant institutional Ethics Committees approved this study. We thank the participants and their families for their kind cooperation, generosity, and patience.

Funding

This study was funded by National High-tech R&D Program (863 Program), No. 2015AA020306, the project of National Basic Research Program of China (to X.M. 2015CB942800), the Nature Science Foundation of China (to X.M. 81361120381. To C.F. 81402446. To T.C, 81201683 and 81672904).

Compliance with ethical standards

Conflict of interest

All authors declare that he/she has no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

432_2017_2417_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Shengliang Zhang
    • 1
  • Yanna Shang
    • 1
  • Tie Chen
    • 2
  • Xin Zhou
    • 1
  • Wengtong Meng
    • 1
  • Chuanwen Fan
    • 3
  • Ran Lu
    • 1
  • Qiaorong Huang
    • 1
  • Xue Li
    • 1
  • Xu Hong
    • 1
  • Zongguang Zhou
    • 3
  • Jiankun Hu
    • 4
    Email author
  • Xianming Mo
    • 1
  1. 1.Laboratory of Stem Cell Biology, State Key Laboratory of BiotherapyWest China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyChengduChina
  2. 2.Health Science Center, Institute of Molecular MedicineShenzhen UniversityShenzhenChina
  3. 3.Department of Gastrointestinal Surgery and Institute of Digestive Surgery, State Key Laboratory of BiotherapyWest China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyChengduChina
  4. 4.Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of BiotherapyWest China Hospital, Sichuan University, and Collaborative Innovation Center of BiotherapyChengduChina

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