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Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation

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Abstract

Purpose

Currently, the interaction between the niche and glioma cancer stem cells (gCSCs) is gaining attention. However, there are few studies concerned with the effects of repeated exposure to a new microenvironment on gCSCs characteristics. In this study, serial in vivo subtransplantation was performed to create a new microenvironment. We evaluated and compared the biological characteristics of gCSCs after serial in vivo subtransplantation.

Methods

We cultured gCSCs from human glioma specimens according to cultured gliomasphere methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By subsequent serial subtransplantation, we obtained first-generation gCSCs (G1-gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro characteristics included the morphology, surface marker profiles, and neural differentiation capacity and the in vivo characteristics was the survival of mice xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and CD31 staining.

Results

We observed no significant differences in the in vitro characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time of mice glioma xenografts was significantly decreased upon serial subtransplantation. In addition, immunohistochemical analyses showed that the number of TUNEL+ cells was significantly decreased while the number of CD31+ cells was significantly increased with serial in vivo subtransplantation.

Conclusions

There were significant in vivo biological changes in gCSCs upon serial in vivo subtransplantation, which were shorter xenograft survival, increased angiogenesis, and decreased apoptosis. This study suggests that the repeated exposure to new microenvironments may affect the biological changes in gCSCs in vivo.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0004506) and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020340).

Conflict of interest

The authors declare no potential conflict of interest.

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Authors and Affiliations

  1. Department of Medical Science, The Catholic University of Korea, Seoul, South Korea

    Ga-Yeong Shin

  2. Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Jin-Kyoung Shim, Ji-Hyun Lee, Eui-Hyun Kim, Eun-Kyung Park, Jong Hee Chang, Dong-Seok Kim, Sun Ho Kim & Seok-Gu Kang

  3. Department of Neurosurgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea

    Hye-Jin Shin & Yong-Kil Hong

  4. Department of Chemistry, Hanyang University, Seoul, South Korea

    Su-Jae Lee

  5. Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Yong-Min Huh

  6. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Se-Hoon Kim

  7. Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Frederick F. Lang

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  1. Ga-Yeong Shin
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  2. Jin-Kyoung Shim
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  15. Frederick F. Lang
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Corresponding author

Correspondence to Seok-Gu Kang.

Additional information

Ga-Yeong Shin and Jin-Kyoung Shim contributed equally to this manuscript.

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Shin, GY., Shim, JK., Lee, JH. et al. Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation. Childs Nerv Syst 29, 55–64 (2013). https://doi.org/10.1007/s00381-012-1963-x

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  • DOI: https://doi.org/10.1007/s00381-012-1963-x

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