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Molecular and Cellular Biochemistry

, Volume 459, Issue 1–2, pp 35–47 | Cite as

Distinct biological characterization of the CD44 and CD90 phenotypes of cancer stem cells in gastric cancer cell lines

  • Xiong Shu
  • Huiqi Liu
  • Yunzhi Pan
  • Lichao Sun
  • Long Yu
  • Lixin Sun
  • Zhihua Yang
  • Yuliang RanEmail author
Article

Abstract

Recent study implicates that gastric cancer stem cells (CSCs) are capable of generating multiple types of cells to promote tumor growth and heterogeneity important for the development of gastric cancer. However, knowledge is limited regarding the expression and characteristics of marker-positive gastric CSCs. Therefore, gastric CSCs from a series of human gastric cancer cell lines (SNU-5, SNU-16, BGC-823, PAMC-82, MKN-45, and NCI-N87) using four putative CSC surface markers (CD44, CD90, CD133, and epithelial-cell adhesion molecule) were investigated the underlying mechanisms regulating such subpopulations. Only SNU-5 and SNU-16 exhibited independent co-expression of CD44+ and CD90+, which exhibited spheroid-colony formation in vitro and tumor formation in immunodeficient mice. Functional studies revealed that CD44+ cells were more invasive compared with CD90+ cells, whereas CD90+ cells exhibited higher levels of proliferation than CD44+ cells. Furthermore, serial xenotransplantation in mice of CD44+/CD90+ cells derived from SNU-5 and SNU-16 revealed rapid growth of CD90+ cells in subcutaneous lesions and a high metastatic capacity of CD44+ cells in the lung. Mechanistic analyses revealed that CD44+ cells underwent epithelial-to-mesenchymal transition (EMT) following acquisition of mesenchymal features, whereas CD90+ cells enhanced the activation of retinoblastoma phosphorylation at Ser780 and oncogenic cell cycle regulators. The expression of CD44 and CD90 in gastric cancer tissues was associated with distant metastasis and the differentiation state of tumors. These results demonstrated that CD44 and CD90 are specific biomarkers capable of identifying and isolating metastatic and tumorigenic CSCs through their ability to regulate EMT and the cell cycle in gastric cancer cell lines.

Keywords

Gastric cancer stem cells CD44 CD90 Metastasis Tumorigenicity 

Notes

Acknowledgements

This study was funded by grants from CAMS Innovation Fund for Medical Sciences (Grant Nos. 2016-I2M-3-013 and 2017-I2M-3-005).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal experiments were approved by The Animal Care and Use Committee of Cancer Hospital, Chinese Academy of Medical Science, and Peking Union Medical College (Beijing, China).

Informed consent

Patients signed informed consent forms for sample collection.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Xiong Shu
    • 1
  • Huiqi Liu
    • 1
  • Yunzhi Pan
    • 1
  • Lichao Sun
    • 1
  • Long Yu
    • 1
  • Lixin Sun
    • 1
  • Zhihua Yang
    • 1
  • Yuliang Ran
    • 1
    Email author
  1. 1.National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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