Somatostatin and Dopamine Receptor Profile of Gastroenteropancreatic Neuroendocrine Tumors: An Immunohistochemical Study

Diakatou, Evanthia; Kaltsas, Gregory; Tzivras, Michail; Kanakis, George; Papaliodi, Eugenia; Kontogeorgos, George

doi:10.1007/s12022-011-9149-8

Cited by 27 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two spliced variants of SSTR2 (SSTR2A and SSTR2B) have been found, with SSTR2A having the highest expression and the greatest relevance from a biological and clinical perspective. Somatostatin and its synthetic analogues (octreotide and lanreotide) act through the five specific SSTRs found on the cell membranes of various tumours, including GEP-NET (Diakatou et al 2011). The first step of the signalling cascade following agonist stimulation is the internalisation of the SSTR (Scott et al 2002).…”

Section: Somatostatin Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Walenkamp¹,

Crespo²,

Maya³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

In the past few years, there have been advances in the treatment of neuroendocrine tumours (NETs) and improvements in our understanding of NET biology. However, the benefits to patients have been relatively modest and much remains yet to be done. The 'Hallmarks of Cancer', as defined by Hanahan and Weinberg, provide a conceptual framework for understanding the aberrations that underlie tumourigenesis and to help identify potential targets for therapy. In this study, our objective is to review the major molecular characteristics of NETs, based on the recently modified 'Hallmarks of Cancer', and highlight areas that require further research.

show abstract

Section: Somatostatin Receptorsmentioning

confidence: 99%

“…Dopamine, a well-characterised neurotransmitter, acts through five dopamine receptors (D1-D5) that are expressed in endocrine tumours (Diakatou et al 2011). The D2 receptor is the most relevant from a clinical perspective.…”

Section: Other Gpcrsmentioning

confidence: 99%

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Walenkamp¹,

Crespo²,

Maya³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…The SSTR subtypes 1-5 are targeted via somatostatin receptor scintigraphy (SRS) and long-acting somatostatin analogues (SAs) [5,6] and/or peptide receptor radionuclide treatment [7] for diagnostic and therapeutic purposes, respectively. To date, only a limited number of studies have demonstrated the expression of SSTR subtypes other than SSTR2A in NETs with divergent results, possibly due to differences in the methodology applied [8,9,10,11,12,13,14,15,16,17,18]. Data concerning LCs are even more sparse and inconsistent [15,18,19,20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

“…This may be attributed to heterodimerization between SSTRs and DRs that result in new oligomeric receptor entities with enhanced functional activity [28]. To date, only few studies have investigated the expression of DR2 in NETs, and only two included a small number of LCs [11,29,30,31,32]. In addition, the co-expression of SSTRs and DRs has not been examined in LCs.…”

Section: Introductionmentioning

confidence: 99%

Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung Carcinoids: Implications for a Therapeutic Role

Kanakis

Grimelius²,

Spathis

et al. 2015

Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

Objective: The expression of somatostatin receptors (SSTRs) and dopamine receptor 2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin analogues and dopamine agonists can be used for their localization and/or treatment. The objective of this study is to examine the expression of the five SSTR subtypes and DR2 in lung carcinoids (LCs). Methods: We conducted a retrospective study of 119 LCs from 106 patients [typical carcinoids (TCs): n = 100, and atypical carcinoids (ACs): n = 19]. The expression of all five SSTR subtypes and DR2 was evaluated immunohistochemically and correlated to clinicopathological data. In a subgroup of cases, receptor expression was further analyzed using semiquantitative RT-PCR. Results: SSTR2A was the SSTR subtype most frequently expressed immunohistochemically (72%), followed by SSTR1 (63%), SSTR5 (40%), and SSTR3 (20%), whereas SSTR4 was negative. DR2 was expressed in 74% and co-expressed with SSTR1 in 56%, with SSTR2A in 59%, with SSTR3 in 19%, and with SSTR5 in 37% of the tumors. Receptor expression was not related to the histological subtype, tumor aggressiveness (disease extent/grading) or functionality; however, DR2 was expressed more frequently in ACs than TCs (95 vs. 70%, p = 0.017). In a subset of patients, RT-PCR findings highly suggested that the expression of SSTR2A, SSTR3, DR2, and to a lesser extent that of SSTR1 and SSTR5 is the outcome of increased gene transcription. Conclusions: The high and variable immunohistochemical expression of the majority of SSTRs along with their co-expression with DR2 in LCs provides a rationale for their possible treatment with agents that target these receptors.

show abstract

“…Such compounds have been shown to be more effective in suppressing growth hormone and prolactin secretion from cultured human growth hormone-secreting pituitary tumors than monoreceptor ligands alone [13,14,15]. As the majority of GEP-NETs coexpress SSTRs and D2R, such compounds might offer novel therapeutic opportunities [16,17]. …”

Section: Introductionmentioning

confidence: 99%

The Novel Somatostatin Receptor 2/Dopamine Type 2 Receptor Chimeric Compound BIM-23A758 Decreases the Viability of Human GOT1 Midgut Carcinoid Cells

Zitzmann

Andersen²,

Vlotides³

et al. 2013

Neuroendocrinology

View full text Add to dashboard Cite

The majority of neuroendocrine tumors (NETs) of the gastroenteropancreatic system coexpress somatostatin receptors (SSTRs) and dopamine type 2 receptors (D2R), thus providing a rationale for the use of novel SSTR2/D2R chimeric compounds in NET disease. Here we investigate the antitumor potential of the SSTR2/D2R chimeric compounds BIM-23A760 and BIM-23A758 in comparison to the selective SSTR2 agonist BIM-23023 and the selective D2R agonist BIM-53097 on human NET cell lines of heterogeneous origin. While having only minor effects on human pancreatic and bronchus carcinoid cells (BON1 and NCI-H727), BIM-23A758 induced significant antitumor effects in human midgut carcinoid cells (GOT1). These effects involved apoptosis induction as well as inhibition of mitogen-activated protein kinase and Akt signaling. Consistent with their antitumor response to BIM-23A758, GOT1 cells showed relatively high expression levels of SSTR2 and D2R mRNA. In particular, GOT1 cells highly express the short transcript variant of D2R. In contrast to BIM-23A758, the SSTR2/D2R chimeric compound BIM-23A760 as well as the individual SSTR2 and D2R agonistic compounds BIM-23023 and BIM-53097 induced no or only minor antitumor responses in the examined NET cell lines. Taken together, our findings suggest that the novel SSTR2/D2R chimeric compound BIM-23A758 might be a promising substance for the treatment of NETs highly expressing SSTR2 and D2R. In particular, a sufficient expression of the short transcript variant of DR2 might play a pivotal role for effective treatment.

show abstract

Somatostatin and Dopamine Receptor Profile of Gastroenteropancreatic Neuroendocrine Tumors: An Immunohistochemical Study

Cited by 27 publications

References 29 publications

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung Carcinoids: Implications for a Therapeutic Role

The Novel Somatostatin Receptor 2/Dopamine Type 2 Receptor Chimeric Compound BIM-23A758 Decreases the Viability of Human GOT1 Midgut Carcinoid Cells

Contact Info

Product

Resources

About