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

 Junseong Park  ;  Dongkyu Lee  ;  Jin-Kyoung Shim  ;  Seon-Jin Yoon  ;  Ju Hyung Moon  ;  Eui Hyun Kim  ;  Jong Hee Chang  ;  Su-Jae Lee  ;  Seok-Gu Kang 
 YONSEI MEDICAL JOURNAL, Vol.64(3) : 157-166, 2023-03 
Journal Title
Issue Date
Animals ; Brain Neoplasms* / genetics ; Brain Neoplasms* / pathology ; Cell Line, Tumor ; Disease Models, Animal ; Glioblastoma* / genetics ; Glioblastoma* / pathology ; Humans ; Neoplasm Invasiveness / genetics ; Neoplastic Stem Cells / metabolism
Glioblastoma ; mesenchymal stem-like cell ; patient-derived tumorsphere ; subventricular zone ; tumor invasion ; ventricle-derived mesenchymal stem-like cells
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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
Moon, Ju Hyung(문주형)
Park, Junseong(박준성)
Yoon, Seon Jin(윤선진) ORCID logo https://orcid.org/0000-0002-3255-5081
Chang, Jong Hee(장종희) ORCID logo https://orcid.org/0000-0003-1509-9800
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