Somatostatin analogs: clinical application in relation to human somatostatin receptor subtypes

Hofland, Leo J.; Visser-Wisselaar, Heleen; Lamberts, Steven W. J.

doi:10.1016/0006-2952(95)00066-9

Cited by 45 publications

(29 citation statements)

References 74 publications

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“…However, there are important differences between the receptor subtypes, which suggest that they may mediate different functions of the native peptide. Each receptor subtype has a distinct tissue distribution, different ligand specificities and is linked to different intracellular coupling systems in addition to adenyl cyclase (reviewed in Hofland et al, 1995). Structurally, the greatest homology is between SSTR2, SSTR3 and SSTR5 on the one hand and SSTR1 and SSTR4 on the other, and these structural homologies translate into similar pharmacological profiles (Serrano et al, 1993).…”

Section: Control Experimentsmentioning

confidence: 99%

“…However, it appears that the five receptor subtypes have a distinct, but overlapping, tissue distribution, unique pharmacological properties and are coupled to a number of intracellular signalling pathways, suggesting that they mediate different functions of the native peptide (Hofland et al, 1995). There is evidence that the direct growth-inhibitory effects of somatostatin are mediated, at least in part, by the activation of intracellular phosphatases (Liebow et al, 1989), and receptor subtypes 1 and 2 have been shown to be coupled to this intracellular pathway (Buscail et al, 1994(Buscail et al, -1995.…”

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confidence: 99%

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Analysis of somatostatin receptor subtype mRNA expression in human breast cancer

Evans

Crook²,

Laws³

et al. 1997

Br J Cancer

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Summary Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue. Receptor expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using receptor subtype-specific primers and by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. A total of 51 breast carcinomas, 36 samples of matched normal tissue, two axillary node metastases and eight normal/benign breast tissue samples were analysed. SSTR2 expression was ubiquitous in both normal and malignant breast tissue. Expression of SSTR5 was detected in approximately one-third of tumour and normal tissue, but fewer than 13% of all tissues expressed SSTR1, 3 and 4. These data suggest that SSTR2 gene expression is ubiquitous in breast cancer. Although this is unlikely to have diagnostic or prognostic significance, SSTR2-specific somatostatin analogues may have therapeutic potential in breast cancer.

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Section: Control Experimentsmentioning

confidence: 99%

mentioning

confidence: 99%

Analysis of somatostatin receptor subtype mRNA expression in human breast cancer

Evans

Crook²,

Laws³

et al. 1997

Br J Cancer

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“…SS binding to SSTR subtypes activates a series of second messenger systems, resulting in the inhibition of calcium channels and adenylate cyclase activity, ultimately leading to inhibition of hormone secretion (Reisine & Bell 1995, Patel 1997, 1999. Stimulation of other second messengers, such as phosphotyrosine phosphatases (PTPs), plays a role in SS-and somatostatin analogs (SSA)-mediated control of cell growth (Schally 1988, Lamberts et al 1991, Hofland et al 1995, Patel 1999, Hofland & Lamberts 2003, Florio 2008, Schonbrunn 2008. Among the SSTR, sst 3 appears to be the subtype mostly related to the pro-apoptotic and antiproliferative effects of SS and SSA (Ferone et al 2002, Hofland & Lamberts 2003.…”

Section: Introductionmentioning

confidence: 99%

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D 2 receptor (D 2 ) have been demonstrated to be effective in controlling hormone secretion and cell proliferation in in vivo and in vitro studies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D 2 as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D 2 pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.

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“…Generally, small neuropeptides, such as somatostatin (SST) and gastrin releasing peptide (GRP)/bombesin (BN) analogues, labelled with g -and/or b --emitting radionuclides are investigated for their ability to bind to receptors which are overexpressed in a variety of malignant tumours [14][15][16]. The affinity of the designed chelator-peptide construct to these receptors may vary depending on the metal incorporated into the complex [17].…”

Section: Introductionmentioning

confidence: 99%