KR158 Spheres Harboring Slow-Cycling Cells Recapitulate High-Grade Glioma Features in an Immunocompetent System.

in Cells by Avirup Chakraborty, Changlin Yang, Jesse L Kresak, Aryeh J Silver, Diana Feier, Guimei Tian, Michael Andrews, Olusegun O Sobanjo, Ethan D Hodge, Mia K Engelbart, Jianping Huang, Jeffrey K Harrison, Matthew R Sarkisian, Duane A Mitchell, Loic P Deleyrolle

TLDR

  • The study looked at cells called glioblastoma stem cells (GSCs) in a mouse model of brain cancer. These cells are important because they can resist treatment and cause the cancer to come back. The study found that cells from the mouse model had similar traits and abilities to human GSCs. The study also found that these cells could form spheres, renew themselves, and cause tumors. The study shows that the mouse model can be used to study GSCs and their role in brain cancer.

Abstract

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

Overview

  • The study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. The KR158 mouse model was used to confirm that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. The study validates the KR158 murine model as a framework to investigate GSCs and SCCs in GBM pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions detailed in the study. The results showed that KR158 murine SCCs exhibited key traits and functional properties akin to human SCCs. The SCCs demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. The study identified significant differences or similarities in the results between these conditions, highlighting the importance of the KR158 murine model in investigating GSCs and SCCs in GBM pathology.

Implications and Future Directions

  • The study's findings have significant implications for the field of research or clinical practice. The KR158 murine model validates as a framework to investigate GSCs and SCCs in GBM pathology, specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections. The study identifies limitations that need to be addressed in future research, such as the need to investigate the role of SCCs in GBM pathogenesis and the development of targeted therapies to target these specific cells. Possible future research directions include exploring the role of SCCs in GBM pathogenesis, developing targeted therapies to target these specific cells, and investigating the effect of immunotherapies on SCCs in GBM.
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