Bombesin,somatostatin and Neurotensin-Like Immunoreactivity in Bronchial Carcinoma

Wood, Susan M.; Wood, J. R.; Ghatei, Mohammad A.; Lee, Y C; O’Shaughnessy, Denis; Bloom, S R

doi:10.1210/jcem-53-6-1310

Cited by 178 publications

(43 citation statements)

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“…Peptides related to bombesin, including gastrin-releasing peptide (GRP) and the neuromedins, are widely distributed in normal mammalian tissues (10)(11)(12)(13)(14)(15)(16) and also are found in high levels in human pulmonary (17)(18)(19)(20) and thyroid (21) tumors. The finding that bombesin is mitogenic (9) and the wide distribution of endogenous mammalian analogues of bombesin strongly suggest that this family of peptides may play a role in the control of both normal and abnormal animal cell growth.…”

mentioning

confidence: 99%

High-affinity receptors for peptides of the bombesin family in Swiss 3T3 cells.

Zachary¹,

Rozengurt²

1985

Proc. Natl. Acad. Sci. U.S.A.

178

134

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Gastrin-releasing peptide (GRP) Peptides related to bombesin, including gastrin-releasing peptide (GRP) and the neuromedins, are widely distributed in normal mammalian tissues (10-16) and also are found in high levels in human pulmonary (17)(18)(19)(20) and thyroid (21) tumors. The finding that bombesin is mitogenic (9) and the wide distribution of endogenous mammalian analogues of bombesin strongly suggest that this family of peptides may play a role in the control of both normal and abnormal animal cell growth.An important step in the elucidation of the mechanism of bombesin-stimulated mitogenesis is to determine the presence of specific receptors for this peptide in Swiss 3T3 cells. We have used biologically active, radiolabeled GRP, the mammalian counterpart of bombesin, to establish the presence of receptors for this molecule.In the present paper, we show that the mitogenic stimulation of Swiss 3T3 cells by peptides of the bombesin family is mediated by a single class of high-affinity receptors. This receptor is distinct from those of other mitogens for these cells. Further, a substance P (SP) analogue recently described as a bombesin antagonist (22) selectively blocks both GRP binding and GRP-induced mitogenesis. Since there is evidence that bombesin-like peptides may contribute to the self-stimulatory (autocrine) growth of small-cell carcinoma of the lung (18-20, 23, 24, 47), our findings may suggest novel clinical approaches to the treatment of this important cancer. MATERIALS AND METHODSCell culture procedures (9,25,26) and assays of DNA synthesis by [3H]thymidine incorporation (26) were carried out as described.Binding Assay. For binding at 37°C, confluent and quiescent cultures of Swiss 3T3 cells in 33-mm dishes were washed twice with Dulbecco's modified Eagle's medium (DME medium) and incubated with 1 ml of binding medium, which consisted of 1:1 (vol/vol) DME and Waymouth media supplemented with 1 mg of bovine serum albumin per ml, 50 mM 2-[bis(2-hydroxyethyl)-2-amino]ethanesulfonic acid (Bes) (pH 7.0), and GRP labeled with 125I at tyrosine-15 at the concentrations indicated. After 30 min of incubation (unless otherwise stated), cultures were washed rapidly four times with cold (4°C) wash solution (0.15 M NaCl/5 mM KCl/0.02 M Na2HPO4/1.8 mM KH2PO4, pH 7.2, supplemented with bovine serum albumin at 1 mg/ml). Washed cultures were extracted in 0.5 ml of 0.1 M NaOH containing 2% Na2CO3 and 1% NaDodSO4, and total cell-associated radioactivity was determined in a y counter. Nonspecific binding, defined as the cell-associated radioactivity not displaced in the presence of 360 nM GRP, was proportional to the concentration of 1251-GRP and varied from 23% of total binding at the highest concentrations (3 nM) of 125I-GRP to 5% at low concentrations (0.05 nM). For binding at 4°C, cells were washed once with DME medium at 4°C and incubated at 4°C for 5 min prior to the binding assay. The binding assay at 4°C was performed in 0.14 M NaCl/5 mM KCl/0.01 M Na2-HPO4/1.8 mM KH2PO4/1.8 mM CaCl2/1 mM MgCl2/25 ...

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confidence: 99%

High-affinity receptors for peptides of the bombesin family in Swiss 3T3 cells.

Zachary¹,

Rozengurt²

1985

Proc. Natl. Acad. Sci. U.S.A.

178

134

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“…It is conceivable that the immunoreactive material is released into the general circulation where it may be implicated in the pathogenesis of paraneoplastic syndromes. Previously, NTLI has been shown to be present in endocrine pancreatic tumours (Blackburn et al, 1980;Feurle et al, 1981;Gutniak et al, 1980;Theodorsson-Norheim et al, 1983) and it also was found in human small cell lung carcinomas (Wood et al, 1981(Wood et al, , 1983. At present, the only cell lines known to produce NTLI have been derived from a rat medullary carcinoma of the thyroid and a rat phaeochromocytoma (Tischler et al, 1982;Zeytinoglu et al, 1980).…”

Section: Resultsmentioning

confidence: 95%

Neurotensin in human small cell lung carcinoma

Goedert¹,

Reeve²,

Emson³

et al. 1984

Br J Cancer

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“…SCLC is known to secrete bombesin-like peptides (20)(21)(22) that might act as autocrine growth factors (2,25). Thus it was plausible but not proven that an antagonist to bombesin/GRP would inhibit SCLC growth, so we tested the effects of peptides A and D on SCLC cells in vitro.…”

Section: Peptide a And Peptide D Inhibit The Growth Of Sclc Cellmentioning

confidence: 99%

“…SCLC constitutes 25% of lung cancers and is, therefore, of major clinical and economic importance. Evidence that bombesin-like peptides, which are secreted by these tumors (20)(21)(22), can act as autocrine growth factors (25) has prompted the search for clinically useful GRP antagonists. We have presented evidence that two peptides that are antagonists of GRP and vasopressin profoundly inhibit the growth of SCLC cells in vitro although the participation of other growthpromoting peptides cannot be excluded.…”

Section: Peptide a And Peptide D Inhibit The Growth Of Sclc Cellmentioning

confidence: 99%