Bombesin-like peptides in small cell lung cancer: Biochemical characterization and secretion from a cell line

Moody, Terry W.; Russell, Edward K.; O’Donohue, Thomas L.; Linden, Carol D.; Gazdar, Adi F.

doi:10.1016/0024-3205(83)90142-x

Cited by 73 publications

(15 citation statements)

References 19 publications

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“…However, the only known mammalian homologue of these peptides, neuromedin B, is not blocked at the amino terminus and contains threonine in its carboxy terminus (17,19). Finally, the presence of serine in both BAL fluid BLP raises the possibility of these being related to the phyllolitorin family (17 The levels of BAL fluid BLP reported here are many fold higher than those reported by other investigators in human plasma (20) and in conditioned media using SCLC cell lines (21). However, comparable levels have been reported in milk (22), and more recently, in urine (23).…”

Section: Resultssupporting

confidence: 67%

Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Aguayo¹,

Kane²,

King³

et al. 1989

J. Clin. Invest.

115

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Bombesin-related peptides are growth factors for a variety of cells, including normal human bronchial epithelial cells. An ELISA for bombesin-like peptides (BLP) has been devised using the MAb BBC353, which is specific for the biologically active carboxy-terminal fragment shared by all known BLP. Using this ELISA, we measured bronchoalveolar lavage (BAL) fluid levels of BLP in normal cigarette smokers (n = 15) and normal nonsmokers (n = 18). Smokers' BAL fluid contained increased levels of BLP, whether expressed in terms of BAL fluid volume (P = 0.0001) or protein content (P < 0.05). BLP levels did not correlate with any cellular constituent in the BAL fluid but immunostaining of lung tissue with BBC353 revealed an intense specific staining of neuroendocrine cells, implying these as a potential source. Two peaks of bombesinlike immunoreactivity were purified using sequential reverse phase and gel filtration HPLC. Both BLP have apparent molecular weights similar to gastrin-releasing peptide on gel filtration HPLC analysis. However, the amino acid composition of these BLP is different from that of gastrin-releasing peptide or neuromedin B, the only known mammalian forms of BLP, suggesting either incomplete purification or novel peptides. Sequence analysis could not be performed due to blocking groups at the amino terminus of these peptides. Our data demonstrate that cigarette smoking is associated with increased levels of pulmonary BLP and imply a potential role for these neuropeptides in the lung's response to tobacco smoke.

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Section: Resultssupporting

confidence: 67%

Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Aguayo¹,

Kane²,

King³

et al. 1989

J. Clin. Invest.

115

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“…The high pressure liquid chromatography data would also be consistent with the possibility that hGRP has an additional amino acid (alanine) at its amino terminus. hGRP contains two potential internal tryptic cleavage sites that could generate hGRP-(14-27) or hGRP- (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Highpressure liquid chromatography of GRP immunoreactivity demonstrates one species consistent with hGRP-(1-27) and a smaller form consistent with either hGRP-(14-27) (17) or hGRP- (18-27) (18, 44).…”

Section: Discussionmentioning

confidence: 99%

“…Bombesinrelated peptides of 10 and 27 amino acids have been isolated from porcine (16) and canine (4) tissues. Analyses by highpressure liquid chromatography of fetal lung (17) and lung tumors (15,18,19) yield multiple peaks of immunoreactivity; one peak elutes near bombesin and one elutes near GRP. Multiple immunoreactive forms are also detected in gastrointestinal tissue (9,20).…”

mentioning

confidence: 99%

Cloning and characterization of cDNAs encoding human gastrin-releasing peptide.

Spindel¹,

Chin

Price

et al. 1984

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

192

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We have prepared and cloned cDNAs derived from poly(A)+ RNA from a human pulmonary carcinoid tumpor rich in immunoreactivity to gastrin-releasing peptide, a peptide closely related in structure to amphibian bombesin.Mixtures of synthetic oligodeoxyribonucleotides corresponding to amphibian bombesin were used as hybridization probes to screen a cDNA library prepared from the tumor RNA. Sequencing of the recombinant plasmids shows that human gastrin-releasing peptide (hGRP) mRNA encodes a precursor of 148 amino acids containing a typical signal sequence, hGRP consisting of 27 or 28 amino acids, and a carboxyl-terminal extension peptide. hGRP is flanked at its carboxyl terminus by two basic amino acids, following a glycine used for amidation of the carboxyl-terminal methionine. RNA blot analyses of tumor RNA show a major mRNA of 900 bases and a minor mRNA of 850 bases. Blot hybridization analyses using human genomic DNA are consistent with a single hGRP-encoding gene. The presence of two mRNAs encoding the hGRP precursor protein in the face of a single hGRP gene raises the possibility of alternative processing of the single RNA transcript.Gastrin-releasing peptide (GRP) is a mammalian equivalent of the amphibian tetradecapeptide bombesin (1). GRP was originally isolated from porcine stomach by using the release of gastrin as a bioassay (2). Peptides related in structure have been isolated from avian proventriculus (3) and canine small intestine (4). Bombesin and the GRPs share similarities in their sequences and contain a common carboxyl-terminal heptapeptide.GRP and bombesin have similar biological effects (5). Infusion of nanogram amounts of either peptide to dogs or humans increases plasma immunoreactive levels of gastrin, pancreatic polypeptide, glucagon, gastric inhibitory peptide, and insulin (5, 6). Bombesin is also a potent neuropeptide; intraventricular injections of 1 pM bombesin into rats elevates blood sugar (7) and produces hypothermia (8). These potent effects coupled with the wide distribution of bombesin-like peptides throughout the mammalian gastrointestinal tract (9) and nervous system (10) support the role of bombesin as an important neuroregulatory peptide.Bombesin-like immunoreactivity is also detected in the neuroendocrine cells of the lung (11). In humans, the highest levels are found in the lung just after birth (12) and levels then decrease in parallel with the observed decrease in the number of pulmonary neuroendocrine cells (13). Bombesin immunoreactivity is also found in high levels in pulmonary carcinoid tumors as well as in many small cell carcinomas of the lung (14, 15). Hence, bombesin-like immunoreactivity is a potential chemical marker for these tumors.As is characteristic of many neuropeptides, mammalian bombesin-like peptides exist in multiple forms. Bombesinrelated peptides of 10 and 27 amino acids have been isolated from porcine (16) and canine (4) tissues. Analyses by highpressure liquid chromatography of fetal lung (17) and lung tumors (15,18,19) yield multiple peaks ...

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“…Somatostatin also suppresses the release of pancreatic and gut hormones and exocrine secretions of the pancreas and stomach (6, 13) and consequently its analogs could be of value for impeding the growth of other cancers, such as pancreatic cancer (13,14,29,31). In addition, the secretion of bombesin and the related peptide gastrin releasing peptide, which are growth factors for small cell lung carcinomas (38)(39)(40), might be reduced by somatostatin. Another possible mechanism by which somatostatin analogs might inhibit tumor growth is the interference with the synthesis of autocrine growth factors by tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer.

Redding¹

1987

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

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Bombesin-like peptides in small cell lung cancer: Biochemical characterization and secretion from a cell line

Cited by 73 publications

References 19 publications

Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.

Cloning and characterization of cDNAs encoding human gastrin-releasing peptide.

Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer.

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