title: Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review.
abstract: 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 meta-analysis 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.
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.|Departments of 2 Neurosurgery.
authors.forename: Thomas
authors.initials: T
authors.lastname: Graillon
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
authors.forename: David
authors.initials: D
authors.lastname: Romano
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
authors.forename: Céline
authors.initials: C
authors.lastname: Defilles
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
authors.forename: Amira
authors.initials: A
authors.lastname: Mohamed
authors.affiliation: Pathology and Brain Pathology, and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.affiliation: Department of Neurosurgery, Hopital Nord, AP-HM, Marseille, France.
authors.forename: Pierre-Hugues
authors.initials: PH
authors.lastname: Roche
authors.affiliation: Departments of 2 Neurosurgery.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fuentes
authors.affiliation: Neuro-oncology, Hopital La Timone, AP-HM; and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.affiliation: Departments of 2 Neurosurgery.
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D000078331:Correlation of Data; D006801:Humans; D066298:In Vitro Techniques; D008579:Meningioma / Q000188:drug therapy*; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide
keywords: BrdU = bromodeoxyuridine; ERK = extracellular regulated kinase; GEP-NET = gastroenteropancreatic neuroendocrine tumor; PBS = phosphate-buffered saline; PCR = polymerase chain reaction; PFS6 = 6-month progression-free survival; SST = somatostatin receptor; SST2; SST2 = SST subtype 2; VEGF = vascular endothelial growth factor; WHO = World Health Organization; mTOR = mammalian target of rapamycin; meningioma; merlin; octreotide; somatostatin; therapy; βGus = β-glucuronidase