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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
The ABCG2 resistance network of glioblastoma
Anne-Marie Bleau1, Jason T Huse, Eric C Holland
1Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Abstract:
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor variant. It exhibits heterogeneity at both the morphologic and genetic levels, with a complex combination of somatic alterations rendering the tumor class difficult to adequately treat. The role of so-called "cancer stem-cells" (CSCs) in the resistance of high-grade gliomas like GBM to conventional treatment regimens has received much recent attention, especially with regard to the enhanced ability of stem-like cells to activate survival pathways, repair DNA damage, and expel cytotoxic drugs. Furthermore, the biology of GBM is actually even more convoluted, characterized by a constantly changing microenvironment that greatly influences tumor growth and response to therapy. Herein we review the most recently reported genetic events in human glioma patients and their influence on treatment response, particularly in relation to O6-methylguanine-DNA methyltransferase methylation status. We aim to present evidence for a role for cancer stem-like cells and their unique microenvironment in therapy resistance and forward our views on glioma initiation and origin. Finally, given the recent interest in "side population" (SP) cells as a model of CSCs in gliomagenesis, we further describe the function of ABCG2 transporters, the mediators of the SP phenotype, at both the blood-brain barrier and in stem-like tumor cells.
Insights
Glioblastoma multiforme (GBM) is a deadly brain tumor. Cancer stem-cells (CSCs) and their microenvironment contribute to treatment resistance, influencing glioma origin and progression.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor.
- Tumor heterogeneity and genetic alterations complicate treatment strategies.
- Cancer stem-cells (CSCs) are implicated in treatment resistance in high-grade gliomas.
Purpose of the Study:
- To review recent genetic events in human gliomas and their impact on treatment response.
- To present evidence for the role of CSCs and their microenvironment in therapy resistance.
- To discuss the function of ABCG2 transporters in side population (SP) cells and gliomagenesis.
Main Methods:
- Literature review of recent genetic events in glioma patients.
- Analysis of the role of CSCs and tumor microenvironment in treatment resistance.
- Description of ABCG2 transporter function in SP cells and the blood-brain barrier.
Main Results:
- CSCs exhibit enhanced survival pathways, DNA repair, and drug efflux mechanisms.
- The GBM microenvironment dynamically influences tumor growth and therapeutic response.
- O6-methylguanine-DNA methyltransferase (MGMT) methylation status is a key factor in treatment response.
Conclusions:
- CSCs and their unique microenvironment are critical factors in GBM therapy resistance.
- Understanding glioma initiation and origin is crucial for developing novel treatments.
- ABCG2 transporters play a significant role in the SP phenotype, relevant to gliomagenesis and blood-brain barrier function.
