Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes

Yang Xiao, Dongjoo Kim, Burak Dura, Kerou Zhang, Runchen Yan, Huamin Li, Edward Han, Joshua Ip, Pan Zou, Jun Liu, Ann Tai Chen, Alexander O. Vortmeyer, Jiangbing Zhou, Rong Fan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.

Original languageEnglish (US)
Article number1801531
JournalAdvanced Science
Volume6
Issue number8
DOIs
StatePublished - Apr 17 2019

Keywords

  • brain tumor dynamics
  • ex vivo assays
  • microvasculature
  • organ-on-a-chip

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Xiao, Y., Kim, D., Dura, B., Zhang, K., Yan, R., Li, H., Han, E., Ip, J., Zou, P., Liu, J., Chen, A. T., Vortmeyer, A. O., Zhou, J., & Fan, R. (2019). Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes. Advanced Science, 6(8), [1801531]. https://doi.org/10.1002/advs.201801531