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ProNGF Expression and Targeting in Glioblastoma Multiforme
Mark Marsland1,2, Amiee Dowdell1,2, Sam Faulkner1,2
1School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
International Journal of Molecular Sciences
|January 21, 2023
Summary
Pro-nerve growth factor (proNGF) is elevated in glioblastoma multiforme (GBM), a deadly brain cancer. Targeting proNGF shows potential for inhibiting GBM cell growth, but does not enhance standard chemotherapy efficacy.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular pathology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with limited treatment options.
- Temozolomide (TMZ) is the standard chemotherapy, but its efficacy is often restricted.
- Nerve growth factor (NGF) and its precursor proNGF are implicated in tumor progression, with proNGF's role in GBM being previously uninvestigated.
Purpose of the Study:
- To investigate the expression and biological activity of proNGF in GBM.
- To determine if proNGF can serve as a biomarker or therapeutic target for GBM.
Main Methods:
- Immunohistochemistry and digital quantification of proNGF in GBM and low-grade glioma patient tissues (n=72 and n=20, respectively).
- Western blotting to detect proNGF in GBM cell lines.
- In vitro studies using anti-proNGF blocking antibodies on GBM cells.
- In vivo studies using subcutaneous xenografts of human GBM cells treated with anti-proNGF antibodies and TMZ.
Main Results:
- ProNGF expression was significantly higher in GBM compared to low-grade gliomas.
- ProNGF was detected in GBM patient plasma and cell lines.
- Anti-proNGF antibodies inhibited GBM cell growth, particularly in cells with methylated MGMT promoter.
- Targeting proNGF did not improve TMZ efficacy in vitro or in vivo; antibodies only slightly reduced tumor volume.
Conclusions:
- ProNGF is overexpressed in GBM and contributes to cancer cell growth.
- ProNGF represents a potential biomarker and therapeutic target for GBM.
- Further research is needed to fully elucidate the clinical utility of targeting proNGF in GBM treatment strategies.
