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Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis
Takeshi Fujimori1, Yuki Shibayama2, Takahiro Kanda3
1Department of Neurological Surgery, Kagawa University Faculty of Medicine, 1750-1 Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. fujimori.takeshi@kagawa-u.ac.jp.
Abstract:
Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/β-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.
Insights
A new monoclonal antibody targeting the (pro)renin receptor [(P)RR] effectively combats glioblastoma. This antibody therapy reduces tumor growth, proliferation, and migration while inducing apoptosis, offering a promising glioblastoma treatment strategy.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Glioblastoma exhibits significant self-renewal and poor differentiation.
- The (pro)renin receptor [(P)RR] has been identified as a potential therapeutic target for glioma.
- Previous studies indicated gene silencing of (P)RR as a viable strategy.
Purpose of the Study:
- To investigate the efficacy of a monoclonal antibody against (P)RR in targeting gliomagenesis.
- To evaluate the antibody's impact on glioblastoma cell lines and stem cell lines.
- To assess the therapeutic potential of (P)RR antibody treatment in preclinical models.
Main Methods:
- In vitro studies utilized human glioma cell lines (U251MG, U87MG) and a glioma stem cell line (MGG23).
- Western blotting assessed Wnt/β-catenin signaling pathway components and stemness markers.
- In vivo studies involved subcutaneous xenografts in nude mice to evaluate tumor growth.
Main Results:
- The (P)RR antibody significantly reduced expression of Wnt signaling pathway components and stemness markers.
- Antibody treatment decreased cell proliferation, sphere formation, and migration, while inducing apoptosis.
- Systemic administration of the (P)RR antibody markedly reduced tumor volume in xenograft models.
Conclusions:
- The (P)RR antibody demonstrates potent anti-glioma activity by targeting key signaling pathways and stemness markers.
- This antibody represents a promising therapeutic strategy for glioblastoma treatment.
- Further investigation into (P)RR-targeted therapies is warranted for glioblastoma management.
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