Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Journal of Neurosurgery Année : 2017

Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review

Résumé

Objective: Meningiomas express somatostatin receptor subtype 2 (SST2), which is targeted by the somatostatin analog octreotide. However, to date, using somatostatin analog therapy for the treatment of these tumors in clinical practice has been debated. This study aims to clarify the in vitro effects of octreotide on meningiomas for precise clinical applications. Methods: The effects of octreotide were analyzed in a large series of 80 meningiomas, including 31 World Health Organization (WHO) Grade II and 4 WHO Grade III tumors, using fresh primary cell cultures to study the impact on cell viability, apoptosis, and signal transduction pathways. Results: SST2 mRNA was detected in 100% of the tested meningiomas at levels similar to those observed in other SST2-expressing tumors, neuroendocrine tumors, or pituitary adenomas. Octreotide significantly decreased cell proliferation in 88% of meningiomas but did not induce cell death. On average, cell proliferation was more inhibited in the meningioma group expressing a high level of SST2 than in the low-SST2 group. Moreover, octreotide response was positively correlated to the level of merlin protein and inversely correlated to the level of phosphorylated p70-S6 kinase, a downstream effector of the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. Octreotide inhibited Akt phosphorylation and activated tyrosine phosphatase without impacting the extracellular regulated kinase (ERK) pathway. Conclusions Octreotide acts exclusively as an antiproliferative agent and does not promote apoptosis in meningioma in vitro. Therefore, in vivo, octreotide is likely to limit tumor growth rather than induce tumor shrinkage. A metaanalysis of the literature reveals an interest in octreotide for the treatment of WHO Grade I tumors, particularly those in the skull base for which the 6-month progression-free survival level reached 92%. Moreover, somatostatin analogs, which are well-tolerated drugs, could be of interest for use as co-targeting therapies for aggressive meningiomas.
Fichier principal
Vignette du fichier
Graillon et al.pdf (4.39 Mo) Télécharger le fichier
Origine : Accord explicite pour ce dépôt

Dates et versions

hal-01478922 , version 1 (06-03-2017)

Identifiants

Citer

Thomas Graillon, David Romano, Céline Defilles, Alexandru Saveanu, Amira Mohamed, et al.. Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review. Journal of Neurosurgery, 2017, 127 (3), pp.660-669. ⟨10.3171/2016.8.JNS16995⟩. ⟨hal-01478922⟩
237 Consultations
360 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More