Skip to Content
Merck
  • Identification of growth hormone receptor as a relevant target for precision medicine in low-EGFR expressing glioblastoma.

Identification of growth hormone receptor as a relevant target for precision medicine in low-EGFR expressing glioblastoma.

Clinical and translational medicine (2022-07-10)
Maïté Verreault, Irma Segoviano Vilchis, Shai Rosenberg, Nolwenn Lemaire, Charlotte Schmitt, Jérémy Guehennec, Louis Royer-Perron, Jean-Léon Thomas, TuKiet T Lam, Florent Dingli, Damarys Loew, François Ducray, Sophie Paris, Catherine Carpentier, Yannick Marie, Florence Laigle-Donadey, Audrey Rousseau, Natascha Pigat, Florence Boutillon, Franck Bielle, Karima Mokhtari, Stuart J Frank, Aurélien de Reyniès, Khê Hoang-Xuan, Marc Sanson, Vincent Goffin, Ahmed Idbaih
ABSTRACT

New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients. 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. 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. This study pioneers a new field of investigation to improve the prognosis of GBM patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human Growth Hormone human, HGH, recombinant, expressed in HEK 293 cells, HumanKine®, suitable for cell culture
Sigma-Aldrich
Laminin from Engelbreth-Holm-Swarm murine sarcoma basement membrane, 1-2 mg/mL in Tris-buffered saline, 0.2 μm filtered, BioReagent, suitable for cell culture