Glioblastoma CD105cells define a SOX2cancer stem cell-like subpopulation in the pre-invasive niche.

in Acta neuropathologica communications by Jiaxin Li, Fredrik Ek, Roger Olsson, Mattias Belting, Johan Bengzon

TLDR

  • The study investigates CD105 cells as a potential Glioblastoma (GBM) subpopulation. GBM is a type of brain tumor that is very aggressive and difficult to treat. CD105 cells are a type of cell that may be involved in the growth and spread of GBM. The study found that CD105 cells are different from other types of cells in GBM and that they may be a potential target for treatment. The study also found that CD105 cells produce certain chemicals that may be involved in the growth and spread of GBM. The study suggests that targeting CD105 cells could be a way to treat GBM and improve patient outcomes.

Abstract

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults. Glioma stem like cells (GSC) represent the highest cellular hierarchy in GBM and have a determining role in tumor growth, recurrence and patient prognosis. However, a better definition of GSC subpopulations, especially at the surgical resection margin, is warranted for improved oncological treatment options. The present study interrogated cells expressing CD105 (CD105) specifically within the tumor front and the pre-invasive niche as a potential GSC subpopulation. GBM primary cell lines were generated from patients (n = 18) and CD105cells were isolated and assessed for stem-like characteristics. In vitro, CD105cells proliferated and enriched in serum-containing medium but not in serum-free conditions. CD105cells were characterized by Nestin, Vimentinand SOX2, clearly distinguishing them from SOX2GCS. GBM CD105cells differentiated into osteocytes and adipocytes but not chondrocytes. Exome sequencing revealed that GBM CD105cells matched 83% of somatic mutations in the Cancer cell line encyclopedia, indicating a malignant phenotype and in vivo xenotransplantation assays verified their tumorigenic potential. Cytokine assays showed that immunosuppressive and protumorigenic cytokines such as IL6, IL8, CCL2, CXCL-1 were produced by CD105cells. Finally, screening for 88 clinical drugs revealed that GBM CD105cells are resistant to most chemotherapeutics except Doxorubicin, Idarubicin, Fludarabine and ABT-751. Our study provides a rationale for targeting tumoral CD105cells in order to reshape the tumor microenvironment and block GBM progression.

Overview

  • The study investigates CD105 cells as a potential Glioblastoma (GBM) subpopulation. GBM is the most common and aggressive primary brain tumor in adults, and Glioma stem-like cells (GSC) are the highest cellular hierarchy in GBM and play a crucial role in tumor growth, recurrence, and patient prognosis. The study aims to define GSC subpopulations, especially at the surgical resection margin, for improved oncological treatment options. CD105 cells were isolated from GBM primary cell lines and assessed for stem-like characteristics. The study found that CD105 cells proliferated and enriched in serum-containing medium but not in serum-free conditions. CD105 cells were characterized by Nestin, Vimentin, and SOX2, distinguishing them from SOX2GCS. GBM CD105 cells differentiated into osteocytes and adipocytes but not chondrocytes. Exome sequencing revealed that GBM CD105 cells matched 83% of somatic mutations in the Cancer cell line encyclopedia, indicating a malignant phenotype. In vivo xenotransplantation assays verified their tumorigenic potential. Cytokine assays showed that immunosuppressive and protumorigenic cytokines such as IL6, IL8, CCL2, CXCL-1 were produced by CD105 cells. Finally, screening for 88 clinical drugs revealed that GBM CD105 cells are resistant to most chemotherapeutics except Doxorubicin, Idarubicin, Fludarabine, and ABT-751. The study provides a rationale for targeting tumoral CD105 cells to reshape the tumor microenvironment and block GBM progression.

Comparative Analysis & Findings

  • The study compared CD105 cells with other GSC subpopulations, specifically SOX2GCS. CD105 cells proliferated and enriched in serum-containing medium but not in serum-free conditions. CD105 cells were characterized by Nestin, Vimentin, and SOX2, distinguishing them from SOX2GCS. GBM CD105 cells differentiated into osteocytes and adipocytes but not chondrocytes. Exome sequencing revealed that GBM CD105 cells matched 83% of somatic mutations in the Cancer cell line encyclopedia, indicating a malignant phenotype. In vivo xenotransplantation assays verified their tumorigenic potential. Cytokine assays showed that immunosuppressive and protumorigenic cytokines such as IL6, IL8, CCL2, CXCL-1 were produced by CD105 cells. Finally, screening for 88 clinical drugs revealed that GBM CD105 cells are resistant to most chemotherapeutics except Doxorubicin, Idarubicin, Fludarabine, and ABT-751. The study found that CD105 cells are a distinct subpopulation of GSCs with unique characteristics and properties that could be targeted for GBM treatment.

Implications and Future Directions

  • The study's findings have significant implications for the field of GBM research and clinical practice. The study provides a rationale for targeting tumoral CD105 cells to reshape the tumor microenvironment and block GBM progression. The study also identifies CD105 cells as a distinct subpopulation of GSCs with unique characteristics and properties that could be targeted for GBM treatment. The study's findings could lead to the development of new GBM treatment options and improve patient outcomes. Future research could focus on developing targeted therapies against CD105 cells, identifying other GSC subpopulations, and exploring the role of CD105 cells in GBM pathogenesis and progression.
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