Visualization of spatiotemporal dynamics of human glioma stem cell invasion

Ryota Tamura, Hiroyuki Miyoshi, Oltea Sampetrean, Munehisa Shinozaki, Yukina Morimoto, Chizuru Iwasawa, Raita Fukaya, Yutaka Mine, Hirotaka Masuda, Tetsuo Maruyama, Minoru Narita, Hideyuki Saya, Kazunari Yoshida, Hideyuki Okano, Masahiro Toda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glioblastoma exhibits phenotypic and genetic heterogeneity, aggressive invasiveness, therapeutic resistance, and tumor recurrence, which can be explained by the existence of glioma stem cells (GSCs). In this study, we visualized the spatiotemporal dynamics of invasion of human GSCs in an orthotopic xenograft mouse model using time-lapse imaging of organotypic brain slice cultures and three-dimensional imaging of optically cleared whole brains. GSCs implanted in the striatum exhibited directional migration toward axon bundles, perivascular area, and the subventricular zone around the inferior horn of the lateral ventricle. GSCs migrated in a helical pattern around axon bundles in the striatum and invaded broadly in both the rostral and caudal directions. GSCs in the corpus callosum migrated more rapidly and unidirectionally toward the contralateral side with pseudopod extension. These characteristics of GSC invasion shared histological features observed in glioblastoma patients. Spatiotemporal visualization techniques can contribute to the elucidation of the mechanisms underlying GSC invasion that may lead to the development of effective therapy for glioblastoma.

Original languageEnglish
Article number45
JournalMolecular brain
Volume12
Issue number1
DOIs
Publication statusPublished - 06-05-2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Tamura, R., Miyoshi, H., Sampetrean, O., Shinozaki, M., Morimoto, Y., Iwasawa, C., Fukaya, R., Mine, Y., Masuda, H., Maruyama, T., Narita, M., Saya, H., Yoshida, K., Okano, H., & Toda, M. (2019). Visualization of spatiotemporal dynamics of human glioma stem cell invasion. Molecular brain, 12(1), [45]. https://doi.org/10.1186/s13041-019-0462-3