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Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review
Thomas Graillon1,2, David Romano1, Céline Defilles1
1Aix-Marseille Université, CNRS, CRN2M, UMR 7286.
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.
Insights
Octreotide, a somatostatin analog, inhibits meningioma cell proliferation by targeting somatostatin receptor subtype 2 (SST2) but does not cause cell death. This suggests octreotide may limit tumor growth rather than shrink tumors in vivo.
Area of Science:
- Neuro-oncology
- Endocrinology
- Molecular Biology
Background:
- Meningiomas express somatostatin receptor subtype 2 (SST2).
- Octreotide targets SST2, but its clinical use in meningioma treatment remains debated.
- Clarifying octreotide's in vitro effects is crucial for precise clinical applications.
Purpose of the Study:
- To investigate the in vitro effects of octreotide on meningioma cell viability, apoptosis, and signal transduction pathways.
- To determine the efficacy of octreotide in a large cohort of meningiomas, including higher-grade tumors.
- To correlate octreotide response with specific molecular markers.
Main Methods:
- Analysis of 80 primary meningioma cell cultures.
- Assessment of cell viability, apoptosis, and signal transduction pathways.
- Detection of SST2 mRNA, merlin protein, and phosphorylated p70-S6 kinase.
Main Results:
- SST2 mRNA was detected in all tested meningiomas.
- Octreotide significantly reduced proliferation in 88% of meningiomas without inducing apoptosis.
- Response correlated with higher SST2 and merlin levels, and lower p70-S6 kinase phosphorylation.
Conclusions:
- Octreotide acts as an antiproliferative agent in meningiomas, not an apoptotic one.
- In vivo, octreotide is likely to limit tumor growth, supporting its use in WHO Grade I tumors.
- Somatostatin analogs show potential as co-targeting therapies for aggressive meningiomas.

