Yonsei Med J.  2023 Mar;64(3):157-166. 10.3349/ymj.2022.0430.

Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor

• Park J
• Lee D
• Shim JK
• Yoon SJ
• Moon JH
• Kim EH
• Chang JH
• Lee SJ
• Kang SG

• KMID: 2539558
• DOI: http://doi.org/10.3349/ymj.2022.0430

Abstract

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 patient-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 experiments.
Results
After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investigated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accelerated 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 vMSLCinduced 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.

Keyword

Glioblastoma; tumor invasion; mesenchymal stem-like cell; subventricular zone; patient-derived tumorsphere; ventricle-derived mesenchymal stem-like cells