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.