Direct Inhibitory Effects of a Somatostatin Analog, SMS 201-995, on AR4-2J Cell Proliferation via Pertussis Toxin-Sensitive Guanosine Triphosphate-Binding Protein-Independent Mechanism*

Viguerie, Nathalie; Tahiri-Jouti, N.; Ayral, Anne Marie; Cambillau, C.; Scemama, Jean-Luc; Bastie, M. J.; Knuhtsen, Svend; Estève, Jean-Pierre; Pradayrol, Lucien; Susini, C.; Vaysse, Nicole

doi:10.1210/endo-124-2-1017

Cited by 102 publications

(52 citation statements)

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“…By way of a positive control, we have shown that RC-160 can inhibit the EGF-induced growth of the AR42J rat acinar cell line. This is consistent with the report by Viguerie et al (1989) who have demonstrated that the somatostatin analogue SMS 201-995 has direct inhibitory effects on AR42J cell proliferation via a mechanism independent of a pertussis toxin sensitive GTPbinding protein.…”

Section: Cellsupporting

confidence: 93%

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Human pancreatic cancer cell lines do not express receptors for somatostatin

Gillespie

Poston²,

Schächter³

et al. 1992

Br J Cancer

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Summary The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with '251-Tyr" somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 ± 0.05 nM and a B.,,, of 2.1 + 0.26 pmoles mg-' protein on AR42J but no displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer.

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Section: Cellsupporting

confidence: 93%

“…The data revealed that AR42J possesses somatostatin receptors which consist of a single class of high affinity binding sites with a Kd (0.20 nM) in the range of that observed by other groups (Viguerie et al, 1989).…”

Section: Cellmentioning

confidence: 62%

Human pancreatic cancer cell lines do not express receptors for somatostatin

Gillespie

Poston²,

Schächter³

et al. 1992

Br J Cancer

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“…Somatostatin acts as a growth inhibitory factor in a variety of normal and tumor cells (2,9,10). We and others have demonstrated that somatostatin and analogues induce the stimulation of a membrane PTPase, which may be involved in the inhibitory effect of these peptides on cell proliferation (9,11,12,38).…”

Section: Discussionmentioning

confidence: 98%

“…Further, the rapid activation of SHP-1 following somatostatin addition in CHO cells coexpressing sst2 and SHP-1 raises the possibility that activation of SHP-1 is the initiating step for sst2 signal transduction leading to inhibition of cell proliferation. These hypothesis are strengthened by the observation that rat pancreatic tumor AR42J cells are sensitive to the antiproliferative effect of somatostatin analogs and highly express sst2 receptors and SHP-1 (10,16,35). Examining SHP-1 expression in cells sensitive to somatostatin analogs would add significantly to these conclusions.…”

Section: Discussionmentioning

confidence: 98%

“…In pancreatic tumor cells, we and others have previously shown that somatostatin and analogues antagonize the mitogenic effect of growth factors acting on tyrosine kinase receptors such as epidermal growth factor (9,10). Although the molecular events leading to the inhibition of cell proliferation are still poorly understood, it has been shown that, after binding to somatostatin receptors, somatostatin analogues cause a rapid stimulation of a membrane proteintyrosine phosphatase (PTPase) 1 activity and dephosphorylate phosphorylated epidermal growth factor receptors (9,11,12) suggesting that a PTPase may participate in the somatostatininduced inhibition of growth factor-mediated mitogenic signal.…”

mentioning

confidence: 97%

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The Tyrosine Phosphatase SHP-1 Associates with the sst2 Somatostatin Receptor and Is an Essential Component of sst2-mediated Inhibitory Growth Signaling

Lopez

Estève

Buscail

et al. 1997

Journal of Biological Chemistry

162

116

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Activation of the somatostatin receptor sst2, a member of the G i protein-coupled receptor family, results in the stimulation of a protein-tyrosine phosphatase activity involved in the sst2-mediated growth inhibitory signal. Here, we report that SHP-1, a cytoplasmic proteintyrosine phosphatase containing two Src homology 2 domains constitutively associated with sst2 as evidence by coprecipitation of SHP-1 protein with sst2, in Chinese hamster ovary cells coexpressing sst2 and SHP-1. Activation of sst2 by somatostatin resulted in a rapid dissociation of SHP-1 from sst2 accompanied by an increase of SHP-1 activity. SHP-1 was phosphorylated on tyrosine in control cells and somatostatin induced a rapid and transient dephosphorylation on tyrosine residues of the enzyme. Stimulation of SHP-1 activity by somatostatin was abolished by pertussis toxin pretreatment of cells. G i␣3 was specifically immunoprecipitated by anti-sst2 and anti-SHP-1 antibodies, and somatostatin induced a rapid dissociation of G i␣3 from sst2, suggesting that G i␣3 may be involved in the sst2⅐SHP-1 complexes. Finally, somatostatin inhibited the proliferation of cells coexpressing sst2 and SHP-1, and this effect was suppressed in cells coexpressing sst2 and the catalytic inactive SHP-1 (C453S mutant). Our data identify SHP-1 as the tyrosine phosphatase associated with sst2 and demonstrate that this enzyme may be an initial key transducer of the antimitogenic signaling mediated by sst2.

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Paracrine interactions between mesothelial and colon-carcinoma cells in a rat model

et al. 1997

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This study used a co‐culture system with Transwell tissue‐culture inserts to investigate the role of primary cultures of rat peritoneal mesothelial cells on the proliferation of rat colon‐carcinoma cells (CC531 cells). Mesothelial cells significantly inhibited the growth of CC531 cells, while, conversely, CC531 cells stimulated the growth of mesothelial cells. Receptor‐binding studies demonstrated the presence of high‐affinity IGF‐I receptors on the mesothelial and CC531 cells. Both cell types also produced IGF‐I, as measured by radioimmunoassay. IGF‐I stimulated DNA synthesis in mesothelial cells, but had no effect on the growth of CC531 cells. In co‐culture, it was found that IGF‐I potentiated the inhibitory effect of mesothelial cells on CC531 cells. The effect of IGF‐I on mesothelial‐cell proliferation was additive to the stimulatory effect of CC531 cells. TGF‐β had no effect on the growth of the CC531 cells, suggesting that this growth (‐inhibitory) factor is not involved in the inhibitory effect of mesothelial cells on CC531 cell growth. The study provides evidence for the existence of a paracrine loop between mesothelial and colon‐carcinoma cells, giving more insight into the basic cellular mechanisms that may modulate the growth of intraperitoneal colon carcinoma. Inhibition of CC531‐cell proliferation by rat mesothelial cells might explain the earlier finding that tumour cells grow poorly in a surgically uncompromised abdomen. Int. J. Cancer 73:885–890, 1997. © 1997 Wiley‐Liss, Inc.

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Direct Inhibitory Effects of a Somatostatin Analog, SMS 201-995, on AR4-2J Cell Proliferation via Pertussis Toxin-Sensitive Guanosine Triphosphate-Binding Protein-Independent Mechanism*

Cited by 102 publications

References 0 publications

Human pancreatic cancer cell lines do not express receptors for somatostatin

Human pancreatic cancer cell lines do not express receptors for somatostatin

The Tyrosine Phosphatase SHP-1 Associates with the sst2 Somatostatin Receptor and Is an Essential Component of sst2-mediated Inhibitory Growth Signaling

Paracrine interactions between mesothelial and colon-carcinoma cells in a rat model

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