MET signaling regulates glioblastoma stem cells
Kyeung Min Joo1, Juyoun Jin, Eunhee Kim
1Cancer Stem Cell Research Center, Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract:
Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target.
Insights
MET signaling is crucial for glioblastoma stem cells (GSCs), driving tumor growth and treatment resistance. Inhibiting MET offers a promising therapeutic strategy for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Glioblastoma multiforme (GBM) harbors glioblastoma stem cells (GSCs) responsible for tumor propagation and resistance.
- Signaling pathways regulating GSCs in GBM remain incompletely understood.
- MET tyrosine kinase promotes survival, proliferation, and invasion in various cancers, including GBM.
Purpose of the Study:
- To investigate the role of MET signaling in regulating glioblastoma stem cells (GSCs).
- To determine if MET activation is essential for the cancer stem cell phenotype in GBM.
- To evaluate MET as a potential therapeutic target in GBM.
Main Methods:
- Identification and characterization of MET-expressing cells in human primary GBM specimens.
- Assessment of clonogenicity, tumorigenicity, and radiation resistance of MET-high cells.
- In vitro and in vivo inhibition of MET signaling in GSCs.
Main Results:
- A distinct population of MET-high cells was identified in perivascular regions of GBM biopsies.
- These MET-high cells exhibited enhanced clonogenicity, tumorigenicity, and radiation resistance.
- MET inhibition disrupted GBM growth and invasiveness in vitro and in vivo.
Conclusions:
- MET activation is a functional requirement for the glioblastoma stem cell phenotype.
- MET signaling plays a critical role in GBM propagation and treatment resistance.
- Targeting MET represents a promising therapeutic strategy for GBM.
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