Expression of Somatostatin Receptor mRNA in Human Meningiomas and their Implication in in vitro Antiproliferative Activity

Abstract

Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes (SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by [3H]-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.

The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies

“…Interestingly, our results were contradictory to recent data in a series of 16 insulinomas, where sst 5 was positively correlated with aggressive tumour behaviours, such as large tumour size, tumours of uncertain behaviour and presence of nuclear atypia (44). In brain tumours (astrocytomas and meninginomas), no relation existed between Ki-67 and sst subtypes in two series (45,46). In contrast, in breast cancer, sst 2 mRNA expression was significantly higher in low-proliferating (as measured using Ki-67) breast cancers (47).…”

Treatment of unresectable skull base meningiomas with somatostatin analogs

“…5,22 About 88% of the meningiomas analyzed (37 of 42 lesions) were positive for at least 1 of the 5 SSTR subtypes, displaying a variable pattern of mRNA expression of the different SSTR subtypes. 2 Messenger RNA from SSTRs 1 and 2 was the most frequently detected, and in half of the meningioma cells 3 or more SSTRs were detected. 2,6 Especially the binding of SST on SSTR2 decreases the production of vascular endothelial growth factor with a reduction in peritumoral edema and is perhaps one factor inhibiting meningioma growth.…”

“…2 Messenger RNA from SSTRs 1 and 2 was the most frequently detected, and in half of the meningioma cells 3 or more SSTRs were detected. 2,6 Especially the binding of SST on SSTR2 decreases the production of vascular endothelial growth factor with a reduction in peritumoral edema and is perhaps one factor inhibiting meningioma growth. 6,21,29 The different receptor subtype binding affinities seem to result in different biological and clinical activities.…”

“…[18][19][20]23,24 One cell proliferation study evaluating a possible role of blocked SSTR in the control of human meningioma cell growth showed a significant inhibition of DNA synthesis in 4 of 5 tissue cultures, and the authors suggested promising effects against meningiomas. 2 In contrast, another analysis showed no direct growth-inhibiting action on cultured human meningioma cells. Rather, there was a slight but significant stimulation of growth in the presence of SST.…”

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors

“…Somatostatin scintigraphy of receptors type 2 with radiolabeled octreotide has been shown to be very useful in the meningioma diagnosis [21][22][23]. In their published study Wang et al showed that 99m Tc-HYNIC-octreotide SPECT/CT SRS is a sensitive method for detecting meningioma [24].…”