Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy

Pasquali, Daniela; Vassallo, Patrizia; Esposito, Dario; Bonavolontà, Giulio; Bellastella, Antonio; Sinisi, A.

doi:10.1677/jme.0.0250063

Cited by 58 publications

(47 citation statements)

References 30 publications

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“…This result is consistent with our previous published data, demonstrating that sst2 expression also triggers apoptosis in the human pancreatic cancer BxPC-3 cells, 10 and with the demonstration of a somatostatin-mediated apoptotic action in the myeloïd cancer HL-60 cells, which only express the subtype 2 of somatostatin receptor. 3 Beside its apoptotic action on cancer cells, somatostatin has also been shown to decrease cell survival in several non-cancer cell models, including intestinal epithelial cells, 4 fibroblasts from Graves' ophtalmopathy 6 and peripheral blood lymphocytes. [7][8][9] However, mechanisms for somatostatin-induced apoptosis and receptor subtype implication were not described in these models.…”

Section: Discussionmentioning

confidence: 99%

“…6,43 Interestingly, the pathogenesis of immunedriven inflammatory disorders, including rheumatoïd arthritis or Graves' disease, is characterized by an excess of fibroblastic-like cell proliferation. The presence of sst2 in Graves' ophtalmopathy fibroblasts may account, at least in part, for the antiproliferative and apoptotic effects of somatostatin in these cells, and for the clinical benefice of somatostatin analogues for the treatment of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of sst2 in Graves' ophtalmopathy fibroblasts may account, at least in part, for the antiproliferative and apoptotic effects of somatostatin in these cells, and for the clinical benefice of somatostatin analogues for the treatment of this disease. 1,6 Materials and Methods Cell culture. Murine fibroblastic NIH3T3 cells were transfected either with the human 1.35-kbp sst2 cDNA (NIH3T3/sst2 cells (clone 2/5 11 ), NIH3T3/sst2.1 cells (clone 2/1 11 )), or with the mock vector (mock cells), and cultured as previously described.…”

Section: Discussionmentioning

confidence: 99%

“…2 Whereas somatostatin effect on cell cycle arrest has been extensively studied, mechanisms for somatostatin-induced apoptosis and receptor subtype implication are only partially elucidated. Somatostatin has been shown to induce cell death in both normal and tumoral cell models [3][4][5][6][7][8][9] . Among the five somatostatin receptors, sst3 and sst2 have been found to play a critical role in somatostatin-induced apoptosis of normal and tumor cells, respectively.…”

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confidence: 99%

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Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

et al. 2006

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Somatostatin is a multifunctional hormone that modulates cell proliferation, differentiation and apoptosis. Mechanisms for somatostatin-induced apoptosis are at present mostly unsolved. Therefore, we investigated whether somatostatin receptor subtype 2 (sst2) induces apoptosis in the nontransformed murine fibroblastic NIH3T3 cells. Somatostatin receptor subtype 2 expression induced an executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B (NF-jB) activity and subsequent inhibition of the mitogenactivated protein kinase JNK. Tumor necrosis factor a (TNFa) stimulated both NF-jB and c-Jun NH2-terminal kinase (JNK) activities, which had opposite action on cell survival. Importantly, sst2 sensitized NIH3T3 cells to TNFa-induced apoptosis by (1) upregulating TNFa receptor protein expression, and sensitizing to TNFa-induced caspase-8 activation; (2) enhancing TNFamediated activation of NF-jB, resulting in JNK inhibition and subsequent executioner caspase activation and cell death. We have here unraveled a novel signaling mechanism for a G protein-coupled receptor, which directly triggers apoptosis and crosstalks with a death receptor to enhance death ligand-induced apoptosis. Somatostatin is a regulatory peptide which is mostly expressed in the central and peripheral nervous system, in the gastro-intestinal tract and in the pancreas. Somatostatin acts via a family of five G protein-coupled receptors (GPCR), somatostatin receptor subtypes 1-5 (sst1-sst5) that are variably expressed throughout numerous tissues ranging from the central nervous system to the endocrine and immune systems. 1 Somatostatin or its analogues promote growth inhibition of various normal and tumor cells, both in vitro and in vivo. Somatostatin affects cell growth indirectly by inhibiting either trophic or growth factor synthesis and/or secretion, or their respective intracellular pathways. Somatostatin antiproliferative action also results from a direct blockade of cell cycle and/or induction of apoptosis. 2 Whereas somatostatin effect on cell cycle arrest has been extensively studied, mechanisms for somatostatin-induced apoptosis and receptor subtype implication are only partially elucidated. Somatostatin has been shown to induce cell death in both normal and tumoral cell models 3-9 . Among the five somatostatin receptors, sst3 and sst2 have been found to play a critical role in somatostatin-induced apoptosis of normal and tumor cells, respectively. 3,5,10 Mechanisms for somatostatin apoptotic action were shown to rely on the mitochondrial pathway through activation either of sst2 or sst3. However, signaling pathways coupling sst2 receptor to apoptosis have been partially elucidated.We have previously demonstrated that expression of sst2 in the nontransformated murine fibroblastic NIH3T3 cells results in a cell growth inhibition, which was dependent on the activation of the tyrosine phosphatase Src homology domain phosphatase-1 (SHP-1). 11 sst2...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

et al. 2006

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“…The presence of sst2 in Graves' ophtalmopathy fibroblasts may account, at least in part, for the antiproliferative and apoptotic effects of somatostatin in these cells, and for the Page 11 of 22 A c c e p t e d M a n u s c r i p t 11 clinical benefice of somatostatin analogs for the treatment of this disease. (Pasquali et al, 2000;Weckbecker et al, 2003).…”

Section: -Inhibition Of Cell Invasion By Somatostatinmentioning

confidence: 99%

Antitumor effects of somatostatin

Pyronnet

Bousquet

Najib

et al. 2008

Molecular and Cellular Endocrinology

159

118

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SummarySince its discovery three decades ago as an inhibitor of GH release from the pituitary gland, somatostatin has attracted much attention because of its functional role in the regulation of a wide variety of physiological functions in the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney and immune system. In addition to its negative role in the control of endocrine and exocrine secretions, somatostatin and analogs also exert inhibitory effects on the proliferation and survival of normal and tumor cells. Over the past 15 years, studies have begun to reveal some of the molecular mechanisms underlying the antitumor activity of somatostatin. This review covers the present knowledge in the antitumor effect of somatostatin and analogs and discusses the perspectives of novel clinical strategies based on somatostatin receptor sst2 gene transfer therapy.

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