Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors.

Abstract

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTRI-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTRI and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors. (J. Clin.

Somatostatin receptor subtypes sst1, sst2, sst3 and sst5expression in human pituitary, gastroentero-pancreatic and mammary tumors

“…Inactive pituitary adenomas have a lower prevalence of the various subtypes than the other tumor types. Our results are generally in agreement with those of several groups using other techniques (Epelbaum et al, 1995;Greenman and Melmed, 1994;Kubota et al, 1994;Miller et al, 1995;Panetta and Patel, 1995).…”

“…One particularity of our results, in comparison with most other reports on human tumor sst (Buscail et al, 1996;Epelbaum et al, 1995;Greenman and Melmed, 1994;Kubota et al, 1994;Miller et al, 1995;Panetta and Patel, 1995), is that direct comparison of ]-octreotide ligand, and the abundance of the different subtype mRNAs, is generally good. Most tumors with octreotide binding sites exhibit sst 2 mRNA, whereas in all cases of octreotide-negative tumors, sst 2 mRNA is absent.…”

“…Most tumors expressed at least one sst subtype, and in more than 80% the sst 2 subtype was expressed. Similar results were reported in human neuroblastomas (Prévost et al, 1996), GEP tumors (Kubota et al, 1994) and pheochromocytomas (Epelbaum et al, 1995). On the other hand, an RT-PCR study has shown lack of sst 2 expression in such tumors as pancreatic adenocarcinomas and advanced colorectal cancers (Buscail et al, 1996).…”

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

“…However, this is a difficult task because sst 1 -sst 5 in vitro detection has been studied with distinctly different methods (polymerase chain reaction [PCR], immunohistochemistry, autoradiography) with often contradictory results (25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours

“…Based on binding studies of the cloned receptors, sstr2 has been suggested to be the main target for octreotide and a prerequisite for tumour imaging. This assumption has been supported by studies comparing octreotide scintigraphy with the expression of sstr subtypes in gastroenteropancreatic endocrine tumours (Kubota et al, 1994;John et al, 1996). However, in these studies only small numbers of each tumour type were analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and correlated with octreotide scintigraphy or somatostatin autoradiography.…”