Neurochemical Research

, Volume 42, Issue 5, pp 1478–1487 | Cite as

Probing the Bi-directional Interaction Between Microglia and Gliomas in a Tumor Microenvironment on a Microdevice

Original Paper
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Abstract

It has been proven that microglia are involved in both early and late stages of glioma progression and contribute substantially to the tumor mass of gliomas. Because no appropriate in vitro or in vivo investigative approach is available, the dynamic interaction between microglia and gliomas during tumor formation remains unclear. In this study, three types of microfluidic assay were developed to examine the outcomes of the dynamic interaction between microglia and gliomas. Co-migration assay and two-dimensional cell co-culture assay have been used to show that microglial BV-2 cells migrate toward C6 glioma cells and inhibit tumor growth during the early stage of tumorigenesis. However, in three-dimensional cell spheres (three-dimensional cell co-culture assay) that contain a large amount of glioma cells, mimicking the late stage of glioma growth, the phagocytosis of microglia was suppressed, which suggests that glioma cells could reeducate classically activated microglia into a tumor-promoting state at some point during tumor progression. Notably, we found that microglia could contribute to tumor invasion and acquisition of the epithelial-mesenchymal transition phenotype in the glioma microenvironment during the early stage and the late stage of tumor progression. In conclusion, we have developed a potential quantitative method for in vitro study of glioma immunity and provided evidence for the duality of glioma-associated microglia.

Keywords

Microfluidic device Microglia Glioma Epithelial-mesenchymal transition Phagocytosis Migration 
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Notes

Acknowledgements

This study was supported by International Science & Technology Cooperation Program of China (No. 2015DFA00740), the Instrument Developing Project of the Chinese Academy of Sciences, Key Laboratory of Separation Science for Analytical Chemistry (Dalian Institute of Chemical Physics, Chinese Academy of Sciences), Natural Science Foundation of Liaoning Province, China (No. 201202050), National Nature Science Foundation of China (No. 81402549).

Compliance with Ethical Standards

Conflict of interest

All the authors declare no conflict of interest in this research.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Rui Gu
    • 1
    • 4
  • Xu Zhang
    • 2
    • 5
  • Ge Zhang
    • 3
  • Tingting Tao
    • 1
    • 2
  • Haibo Yu
    • 5
  • Lianqing Liu
    • 5
  • Ying Dou
    • 1
  • Aiping Li
    • 1
  • Jianhua Qin
    • 2
  1. 1.Department of PhysiologyDalian Medical UniversityDalianChina
  2. 2.Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianChina
  3. 3.Department of ImmunologyDalian Medical UniversityDalianChina
  4. 4.Center Laboratory DepartmentGeneral Hospital of Chengdu ArmyChengduChina
  5. 5.State key Laboratory of Robotics, Shenyang Institute of AutomationChinese Academy of SciencesShenyangChina

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