Visualization of spatiotemporal dynamics of human glioma stem cell invasion

• Published in: Molecular brain Vol. 12; no. 1; p. 45
• Main Authors: Tamura, Ryota, Miyoshi, Hiroyuki, Sampetrean, Oltea, Shinozaki, Munehisa, Morimoto, Yukina, Iwasawa, Chizuru, Fukaya, Raita, Mine, Yutaka, Masuda, Hirotaka, Maruyama, Tetsuo, Narita, Minoru, Saya, Hideyuki, Yoshida, Kazunari, Okano, Hideyuki, Toda, Masahiro
• Format: Journal Article
• Language: English
• Published: England BioMed Central 06.05.2019; BMC
• Subjects: Animals; Brain - pathology; Brain cancer; Brain Neoplasms - pathology; Brain slice culture; Brain slice preparation; Cell adhesion & migration; Cell culture; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Corpus callosum; Female; Glioblastoma; Glioma; Glioma - pathology; Glioma cells; Glioma stem cell; Growth factors; Humans; Imaging, Three-Dimensional; Invasion; Invasiveness; Laboratory animals; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplastic Stem Cells - pathology; Neostriatum; Neuroimaging; Neurosciences; Proteins; Stem cell transplantation; Stem cells; Subventricular zone; Time-Lapse Imaging; Tissue clearing; Tumors; Ventricle; Ventricles (cerebral); Visualization; Xenografts; United States > US; Japan; Germany; Tissue clearing; Brain slice culture; Glioma stem cell; Time-lapse imaging; Invasion; Glioblastoma
• ISSN: 1756-6606; 1756-6606
• DOI: 10.1186/s13041-019-0462-3

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.