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KMID : 0311120230640030157
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Yonsei Medical Journal
2023 Volume.64 No. 3 p.157 ~ p.166
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Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor
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Park Jun-Seong
Lee Dong-Kyu
Shim Jin-Kyoung
Yoon Seon-Jin
Moon Ju-Hyung
Kim Eui-Hyun
Chang Jong-Hee
Lee Su-Jae
Kang Seok-Gu
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Abstract
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Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM pa tient-derived cells.
Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo ex periments.
Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investi gated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accel erated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLC induced increases in the invasiveness of GBM TSs.
Conclusion: Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.
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KEYWORD
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Glioblastoma, tumor invasion, mesenchymal stem-like cell, subventricular zone, patient-derived tumorsphere, ventricle-derived mesenchymal stem-like cells
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