Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor.
Yonsei Med J
; 64(3): 157-166, 2023 Mar.
Article
en En
| MEDLINE
| ID: mdl-36825341
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 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Glioblastoma
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Yonsei Med J
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Corea del Sur