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Isolated cancer stem cells from human liver cancer: morphological and functional characteristics in primary culture

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Abstract

Background

Primary liver cancer cells (PLCs) could more directly simulate the human tumor microenvironment. Compared with liver cancer cell lines, PLCs could reflect the human situation. As in previous studies, tumor stem cells were a small number of cancer cells in the microenvironment and considered to be one of the origins of liver cancer. This study aimed to screen stem cells in PLCs, analyze their biological characteristics, propose the possibility that liver cancer originated from stem cells.

Methods

Liver cancer tissues of 17 patients were taken from the Affiliated Hospital of Guangdong Medical College, and PLCs were isolated by tissue slice method. The proliferation, tumor formation in nude mice, stem protein expression of PLCs were observed. C-kit+ liver cancer cells were screened and their biological characteristics were analyzed.

Results

PLCs could be stably passaged. Transmission electron microscopy indicated that the nucleus was irregular, there were many mitochondria, and the endoplasmic reticulum was irregularly distributed. PLCs could express E-Cadherin, Oct-4, β-Catenin, Sox2, CD326, C-kit, GPC3, Nanog. The proliferation curve of PLCs and Hep3B cells were similar, and they all could form tumors in nude mice. Flow-sorted C-kit+ PLCs, as well as C-kit+ Hep3B cells could highly express Bmi1, Sox2, Oct4, Notch1, Nanog, C-kit, β-Catenin, Smo, Nestin, ABCG2, ABCB1. And they also could clone and form tumors in vivo. But C-kit+ PLCs were more sensitive to chemotherapy drugs than C-kit+ liver cancer cell lines.

Conclusion

C-kit+ PLCs had the characteristics of tumor stem cells and were more sensitive to chemotherapy drugs.

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Acknowledgements

We gratefully acknowledge the participation of our patient.

Funding

This research was supported by the Jinan University Scientific Research Cultivation and Innovation Fund (Youth Fund Project: 11619356) and Flagship specialty construction project-General surgery (Funding No.: 711003).

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Author notes

  1. M. Hu and M. Li have contributed equally to the present work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Jinan University First Affiliated Hospital, Guangzhou, 510630, China

    M. Hu

  2. Laboratory of Hepatobiliary Surgery and Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China

    M. Hu, M. Li, H. Huang & C. Lu

Authors
  1. M. Hu
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  2. M. Li
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  3. H. Huang
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  4. C. Lu
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Contributions

MH written this article, ML supplied the study conception, and HH edited pictures. All authors read and approved the manuscript.

Corresponding author

Correspondence to M. Hu.

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Conflict of interest

The authors declare no potential conflicts of interest. The authors state that all data generated during this study are included in this published article.

Ethical approval

The study was approved by the ethics committee of affiliated hospital of guangdong medical university.

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All patients provided informed consent for the use of their data for research purposes.

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Hu, M., Li, M., Huang, H. et al. Isolated cancer stem cells from human liver cancer: morphological and functional characteristics in primary culture. Clin Transl Oncol 24, 48–56 (2022). https://doi.org/10.1007/s12094-021-02667-w

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