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Updated: Jul 3, 2025

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
ABCC4 suppresses glioblastoma progression and recurrence by restraining cGMP-PKG signalling
Jung-Ying Chiang1,2, Sung-Tai Wei3,4, Huan-Jui Chang1,5
1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Background:
Cyclic nucleotides are critical mediators of cellular signalling in glioblastoma. However, the clinical relevance and mechanisms of regulating cyclic nucleotides in glioblastoma progression and recurrence have yet to be thoroughly explored.
Methods:
In silico, mRNA, and protein level analyses identified the primary regulator of cyclic nucleotides in recurrent human glioblastoma. Lentiviral and pharmacological manipulations examined the functional impact of cyclic nucleotide signalling in human glioma cell lines and primary glioblastoma cells. An orthotopic xenograft mice model coupled with aspirin hydrogels verified the in vivo outcome of targeting cyclic nucleotide signalling.
Results:
Elevated intracellular levels of cGMP, instead of cAMP, due to a lower substrate efflux from ATP-binding cassette sub-family C member 4 (ABCC4) is engaged in the recurrence of glioblastoma. ABCC4 gene expression is negatively associated with recurrence and overall survival outcomes in glioblastoma specimens. ABCC4 loss-of-function activates cGMP-PKG signalling, promoting malignancy in glioblastoma cells and xenografts. Hydrogels loaded with aspirin, inhibiting glioblastoma progression partly by upregulating ABCC4 expressions, augment the efficacy of standard-of-care therapies in orthotopic glioblastoma xenografts.
Conclusion:
ABCC4, repressing the cGMP-PKG signalling pathway, is a tumour suppressor in glioblastoma progression and recurrence. Aspirin hydrogels impede glioblastoma progression through ABCC4 restoration and constitute a viable translational approach.
Insights
ATP-binding cassette sub-family C member 4 (ABCC4) acts as a tumor suppressor in glioblastoma by inhibiting cyclic guanosine monophosphate (cGMP) signaling. Aspirin hydrogels restore ABCC4, impeding glioblastoma progression and recurrence.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular signaling
Background:
- Cyclic nucleotides regulate glioblastoma (GBM) cell signaling.
- Mechanisms controlling cyclic nucleotides in GBM progression remain unclear.
Purpose of the Study:
- Identify the primary regulator of cyclic nucleotides in recurrent GBM.
- Investigate the functional role of cyclic nucleotide signaling in GBM.
- Evaluate therapeutic strategies targeting cyclic nucleotide pathways.
Main Methods:
- In silico, mRNA, and protein analyses.
- Lentiviral and pharmacological manipulations in glioma cell lines.
- Orthotopic xenograft mouse models with aspirin hydrogels.
Main Results:
- Reduced ATP-binding cassette sub-family C member 4 (ABCC4) expression elevates intracellular cyclic guanosine monophosphate (cGMP), promoting GBM recurrence.
- ABCC4 loss-of-function activates cGMP-protein kinase G (PKG) signaling, increasing malignancy.
- Aspirin hydrogels upregulate ABCC4, inhibiting tumor progression and enhancing standard therapies.
Conclusions:
- ABCC4 functions as a tumor suppressor in GBM by inhibiting the cGMP-PKG pathway.
- Targeting ABCC4 with aspirin hydrogels represents a promising therapeutic strategy for GBM.
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