Dedifferentiated Cells Obtained from Glioblastoma Cell Lines Are an Easy and Robust Model for Mesenchymal Glioblastoma Stem Cells Studies

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2023 May 11

PMID 37168329

Authors

Cecile Doualle

Julien Gouju

Yousra Nouari

Meline Wery

Clelia Guittonneau

Philippe Codron

Audrey Rousseau

Patrick Saulnier

Joel Eyer

Franck Letournel

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is an aggressive brain tumor with a poor prognosis. Glioblastoma Stem Cells (GSC) are involved in glioblastoma resistance and relapse. Effective glioblastoma treatment must include GSC targeting strategy. Robust and well defined GSC models are required for new therapies evaluation. In this study, we extensively characterized 4 GSC models obtained by dedifferentiation of commercially available glioblastoma cell lines and compared them to 2 established patient derived GSC lines (Brain Tumor Initiating Cells). Dedifferentiated cells formed gliospheres, typical for GSC, with self-renewal ability. Gene expression and protein analysis revealed an increased expression of several stemness associated markers such as A2B5, integrin α6, Nestin, and . Cells were oriented toward a mesenchymal GSC phenotype as shown by elevated levels of mesenchymal and EMT related markers (CD44, , integrin α5). Dedifferentiated GSC were similar to BTIC in terms of size and heterogeneity. The characterization study also revealed that CXCR4 pathway was activated by dedifferentiation, emphasizing its role as a potential therapeutic target. The expression of resistance-associated markers and the phenotypic diversity of the 4 GSC models obtained by dedifferentiation make them relevant to challenge future GSC targeting therapies.

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