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Updated: Sep 5, 2025
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Identification of growth hormone receptor as a relevant target for precision medicine in low-EGFR expressing
Maïté Verreault1, Irma Segoviano Vilchis1, Shai Rosenberg2
1Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
Objective:
New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients.
Methods:
With the objective of identifying alternative oncogenic mechanisms to abnormally activated epidermal growth factor receptor (EGFR) signalling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samples. We then conducted gain of function as well as genetic and pharmocological inhibition assays in GBM patient-derived cell lines to functionnally validate our finding.
Results:
We identified that growth hormone receptor (GHR) signalling defines a distinct molecular subset of GBMs devoid of EGFR overexpression. GHR overexpression was detected in one third of patients and was associated with low levels of suppressor of cytokine signalling 2 (SOCS2) expression due to SOCS2 promoter hypermethylation. In GBM patient-derived cell lines, GHR signalling modulates the expression of proteins involved in cellular movement, promotes cell migration, invasion and proliferation in vitro and promotes tumourigenesis, tumour growth, and tumour invasion in vivo. GHR genetic and pharmacological inhibition reduced cell proliferation and migration in vitro.
Conclusion:
This study pioneers a new field of investigation to improve the prognosis of GBM patients.
Insights
Growth hormone receptor (GHR) signaling drives a subset of glioblastoma (GBM) tumors, offering new therapeutic targets. Inhibiting GHR shows promise in reducing GBM cell proliferation and migration, potentially improving patient outcomes.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma (GBM) remains a challenging brain tumor with poor prognosis.
- Epidermal growth factor receptor (EGFR) signaling is a common driver, necessitating alternative therapeutic targets.
Purpose of the Study:
- To identify novel oncogenic mechanisms in GBM beyond EGFR.
- To investigate the role of growth hormone receptor (GHR) signaling in GBM pathogenesis.
Main Methods:
- Comparative gene expression profiling of 54 human GBM samples.
- Gain-of-function and inhibition assays in patient-derived GBM cell lines.
- In vitro and in vivo functional validation of GHR signaling.
Main Results:
- Identified a distinct GBM molecular subset characterized by GHR overexpression and low SOCS2 levels.
- GHR signaling promotes GBM cell migration, invasion, proliferation, tumorigenesis, and tumor growth.
- GHR inhibition reduced GBM cell proliferation and migration in vitro.
Conclusions:
- GHR signaling represents a novel therapeutic target for a subset of GBM patients.
- This discovery opens a new avenue for improving GBM treatment strategies.
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