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

Abstract

Using in situ hybridization techniques with selective oligoprobes, the gene expression of sst 1 , sst 2 , sst 3 and sst 5 was studied in a series of 32 human pituitary adenomas, 28 breast tumors and 21 endocrine gastroentero-pancreatic tumors, shown to express somatostatin receptors to variable extents. In most of these tumors the sst 2 receptor subtype was abundantly expressed, even though a significant number of pituitary adenomas, breast and gastroentero-pancreatic tumors expressed sst 1 and/or sst 3 as well. A very high incidence of the sst 5 subtype was found in growth hormone-producing pituitary adenomas and, to a lesser extent, in inactive pituitary adenomas, whereas breast tumors seldom expressed sst 5 ; gastroentero-pancreatic tumors showed all possible combinations of sst expression, with, however, a predominance of sst 2 and sst 1 . Overall, the presence of sst 2 mRNA and/or sst 5 mRNA generally correlated with the presence of octreotide binding sites. A lack of octreotide binding sites corresponded with a lack of sst 2 mRNA. Several tumors exhibiting a low number of octreotide binding sites had no measurable sst 2 mRNA, despite abundance of b-actin mRNA, suggesting in these cases a very low abundance of sst mRNAs or a too low sensitivity of the in situ hybridization methodology. In all other cases, the method allowed precise localization of the respective mRNAs on the tumor tissue, notably in breast tumors with non-homogeneous receptor distribution. Tumors without measurable amounts of somatostatin receptors had no detectable sst mRNA. Our results indicate a highly variable abundance of the various sst mRNAs in individual somatostatin receptor-containing tumors.

Somatostatin–dopamine ligands in the treatment of pituitary adenomas

“…a In mixed GH+PRL adenomas b Only in 50% of tumors c mRNA expression in less than 20% of analyzed tumors each receptor were selected. All four compounds displayed an very high affinity for sst2 (IC 50 10-100 pmol/L). In the six tumors treated with these compounds, in cell culture, GH secretion was suppressed with an EC 50 significantly lower than that achieved with octreotide (1 to 10 pmol/L vs. 80 pmol/L).…”

Comparison of 68Ga-DOTATATE and 68Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours

“…An important common feature of these tumours is the expression of various neuroendocrine markers within the tumour cells and secretion of biologically active peptides and amines, which causes symptoms named carcinoid syndrome. Another characteristic feature of these tumours is the overexpression of somatostatin receptors (SSTR) [2]. Up to now five different SSTR (SSTR1-5) subtypes have been identified and NETs have relatively high expression of SSTR2 which makes them ideal targets for functional imaging with radiolabelled somatostatin (SST) analogues and radionuclide therapy [3].…”

Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1–5 and correlation with receptor protein expression and tumor pathology

“…Previous studies have demonstrated the presence of SSTRs in a large variety of tumors and cancer cell lines [12][13][14][15][16][17][18]. Breast cancers express both SST and SSTRs.…”