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Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review
- Source :
- Journal of Neurosurgery, Journal of Neurosurgery, American Association of Neurological Surgeons, 2017, 127 (3), pp.660-669. ⟨10.3171/2016.8.JNS16995⟩, Journal of Neurosurgery, 2017, 127 (3), pp.660-669. ⟨10.3171/2016.8.JNS16995⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- OBJECTIVEMeningiomas 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.METHODSThe 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.RESULTSSST2 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.CONCLUSIONSOctreotide 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.
- Subjects :
- medicine.medical_specialty
[SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Antineoplastic Agents, Hormonal
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Somatostatin Analog Therapy
Octreotide
[SDV.CAN]Life Sciences [q-bio]/Cancer
In Vitro Techniques
Neuroendocrine tumors
somatostatin
meningioma
Meningioma
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Internal medicine
Tumor Cells, Cultured
Humans
Medicine
Correlation of Data
merlin
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
therapy
business.industry
Somatostatin receptor
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
General Medicine
medicine.disease
3. Good health
Somatostatin
Endocrinology
030220 oncology & carcinogenesis
Cancer research
business
030217 neurology & neurosurgery
octreotide
medicine.drug
SST2
Subjects
Details
- Language :
- English
- ISSN :
- 00223085
- Database :
- OpenAIRE
- Journal :
- Journal of Neurosurgery, Journal of Neurosurgery, American Association of Neurological Surgeons, 2017, 127 (3), pp.660-669. ⟨10.3171/2016.8.JNS16995⟩, Journal of Neurosurgery, 2017, 127 (3), pp.660-669. ⟨10.3171/2016.8.JNS16995⟩
- Accession number :
- edsair.doi.dedup.....f67c605f6c463bc506e949b5606f023b