Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels

Reubi, Jean Claude; Schaer, Jean‐Claude; Laissue, Jean A.; Waser, Beatrice

doi:10.1016/s0026-0495(96)90077-3

Cited by 106 publications

(81 citation statements)

References 3 publications

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“…Our results support previous in vivo and in vitro findings on the preferential expression of sst 2 in activated endothelial cells (Reubi et al, 1994(Reubi et al, , 1996(Reubi et al, , 2001ten Bokum et al, 1999;Koizumi et al, 2002). The finding that both sst 5 mRNA and positive immunostaining for sst 5 were expressed in HUVECs, and altered with proliferative status, is novel and indicates that both the mRNA and the protein are expressed in proliferation.…”

Section: Discussionsupporting

confidence: 90%

“…Proliferating endothelium in vitro express sst 2 that is also expressed by endothelial cells within or adjacent to tumours (Reubi et al, 1994(Reubi et al, , 1996(Reubi et al, , 2001ten Bokum et al, 1999, Watson et al, 2001Koizumi et al, 2002), and it has been shown that sst 2 is expressed in the angiogenic sprouts of endothelium from placental veins (Watson et al, 2001). Experimental angiogenesis has been inhibited by the synthetic sst analogue Octreotide (Woltering et al, 1991;Danesi and Del Tacca, 1996;Danesi et al, 1997) that has a high affinity for sst 2.…”

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confidence: 99%

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Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

Adams

Lindow

et al. 2005

Br J Cancer

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Angiogenesis is characterised by activation, migration and proliferation of endothelial cells and is central to the pathology of cancer, cardiovascular disease and chronic inflammation. Somatostatin is an inhibitory polypeptide that acts through five receptors (sst 1, 2, 3, 4, 5). Sst has previously been reported in endothelium, but their role remains obscure. Here, we report the expression of sst in human umbilical vein endothelial cells (HUVECs) in vitro, during proliferation and quiescence. A protocol for culturing proliferating and quiescent HUVECs was established, and verified by analysing cell cycle distribution in propidium-iodide-stained samples using flow cytometry. Sst mRNA was then quantified in nine proliferating and quiescent HUVEC lines using quantitative reverse transcriptase -polymerase chain reaction. Sst 2 and 5 were preferentially expressed in proliferating HUVECs. All samples were negative for sst 4. Sst 1 and 3 expression and cell cycle progression were unrelated. Immunostaining for sst 2 and 5 showed positivity in proliferating but not quiescent cells, confirming sst 2 and 5 protein expression. Inhibition of proliferating cells with somatostatin analogues Octreotide and SOM230, which have sst 5 activity, was found (Octreotide 10 À10 -10 À6 M: 48.5 -70.2% inhibition; SOM230 10 À9 -10 À6 M: 44.9 -65.4% inhibition) in a dose-dependent manner, suggesting that sst 5 may have functional activity in proliferation. Dynamic changes in sst 2 and 5 expression during the cell cycle and the inhibition of proliferation with specific analogues suggest that these receptors may have a role in angiogenesis.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

Adams

Lindow

et al. 2005

Br J Cancer

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“…Moreover, also lung NET, both well-and poorly differentiated, have been shown to express SSTR in vivo, being subtypes 2, 3, and 5 the most represented (Berenger et al 1996, Reubi et al 1996, 1998b, Janson et al 1998, Reisinger et al 1998, Hofland et al 1999, Papotti et al 2000. A recent study evaluating the tissue distribution of sst 2A and sst 3 in a large series (O200 cases) of pulmonary NET with clinically aggressive features (Righi et al 2010) confirmed previous data from small series, showing a decrease in the expression of sst 2 and sst 3 from lowgrade/intermediate-grade to high-grade tumors, and confirming a good correlation between immunohistochemical results and octreotide scintigraphy (Reisinger et al 1998, Granberg et al 2003, Reubi & Waser 2003.…”

Section: Sstr Expression In Endocrine Tumorsmentioning

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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“…The demonstration of expression of SRIF receptors on stromal cells within ovarian tumours means that SRIF analogues could potentially alter tumour growth indirectly, by inhibiting stromal cell production of growth factors. SRIF receptors have been described in both normal human blood vessels (Curtis et al, 2000) and veins surrounding human cancers (Reubi et al, 1994(Reubi et al, , 1996. IGF-1 stimulates growth of new blood vessels in experimental systems (Nakao-Hayashi et al, 1992) and potentially SRIF analogues may inhibit tumour growth indirectly by decreasing IGF-1 production.…”

Section: Discussionmentioning

confidence: 99%

“…IGF-1 stimulates growth of new blood vessels in experimental systems (Nakao-Hayashi et al, 1992) and potentially SRIF analogues may inhibit tumour growth indirectly by decreasing IGF-1 production. As SRIF receptors are expressed on peritumoral vessels they may act directly to inhibit angiogenesis or affect tumour biology by causing vasoconstriction and thus decreasing tumour blood flow (Reubi et al, 1996). The post-receptor signal transduction pathways in octreotide-induced inhibition of angiogenesis have been studied in the chick embryo system and have been shown to depend on G proteins, calcium and cyclic adenosine monophosphate (Patel et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Localisation of somatostatin and somatostatin receptors in benign and malignant ovarian tumours

et al. 2002

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Somatostatin has been identified as having anti-proliferative, anti-angiogenic and pro-apoptotic actions in many tumour systems, and these effects are mediated through a family of five transmembrane G-protein coupled SRIF receptors. Ovarian cancer is the commonest gynaecological malignancy in the UK and maintenance therapy is urgently required. Native somatostatin expression and its receptors sst 1,2,3 and 5 were studied with immunohistochemistry in 63 malignant and 35 benign ovarian tumours of various histological types. Fifty-seven out of 63 (90%) of malignant and 26/35 (74%) benign tumours expressed somatostatin. Receptors sst 1,2,3 and 5 were expressed variably in epithelial, vascular and stromal compartments for both benign and malignant tumours. Somatostatin was found to correlate significantly with stromal sst 1 (P=0.008), epithelial sst 1 (P50.001), stromal sst 2 (P=0.019), vascular sst 2 (P=0.026), epithelial sst 3 (P=0.026), stromal sst 5 (P=0.013) and vascular sst 5 (P=0.038). Increased expression of native somatostatin correlating with somatostatin receptors in malignant ovarian tumours raises the possibility that either synthetic somatostatin antagonists or receptor agonists may have therapeutic potential.

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Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels

Cited by 106 publications

References 3 publications

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Localisation of somatostatin and somatostatin receptors in benign and malignant ovarian tumours

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