The release of bombesin-like peptides from small cell lung cancer cells

Our plain-English summary of The release of bombesin-like peptides from small cell lung cancer cells, by T.W. Moody, L.Y. Korman (Annals of the New York Academy of Sciences, 1988).

The study

• Authors: T.W. Moody, L.Y. Korman
• Journal: Annals of the New York Academy of Sciences
• Published: 1988;547:351-9
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.

In plain English

This conference paper described laboratory and patient work on bombesin-like peptides in small cell lung cancer (SCLC). Part of it drew on earlier published work. It did not study asbestos exposure. All 32 classic SCLC cell lines tested contained the peptides (0.1 to 18.3, mean 0.9 pmol/mg cell protein). None were detected in variant SCLC or in the four adenocarcinoma, two mesothelioma, one large cell carcinoma and one squamous cell carcinoma cell lines. In cell line NCI-H345, vasoactive intestinal peptide (VIP) raised peptide secretion about 3-fold and cyclic AMP about 10-fold. Somatostatin reversed the VIP-driven rise in secretion. In one patient with extensive SCLC, a secretin injection raised plasma levels about 10-fold to 500 pM; the paper's own summary section gives 7-fold. The peptides were detected in the spinal fluid of 7 of 9 patients with meningeal carcinomatosis, 4 of 18 with parenchymal metastases and 1 of 15 controls. The authors concluded that bombesin receptor antagonists may serve as useful agents to inhibit SCLC growth.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Conference paper combining laboratory cell-line experiments with measurements in patients' blood and spinal fluid; part of the work draws on earlier published studies
• Who was studied: Human lung cancer cell lines: 32 classic SCLC, 6 variant SCLC, 8 lung carcinoid, 4 adenocarcinoma, 1 large cell carcinoma, 2 mesothelioma and 1 squamous cell carcinoma. Plasma from SCLC patients, including one with extensive disease given secretin. Spinal fluid from 18 SCLC patients with parenchymal metastases, 9 with meningeal carcinomatosis and 15 controls. Authors were based in Washington, D.C.; study dates were not given.
• Exposure: No asbestos exposure was studied. The agents tested were vasoactive intestinal peptide (VIP), somatostatin (SRIF) and related analogs on cell lines, and secretin (2 units/kg) injected into a patient.
• Main results:
  • All 32 classic SCLC cell lines had detectable bombesin-like peptides, ranging from 0.1 to 18.3 with a mean of 0.9 pmol/mg cell protein.
  • Bombesin-like peptides were not detected in the two mesothelioma cell lines, nor in the adenocarcinoma, large cell carcinoma and squamous cell carcinoma lines tested.
  • In SCLC cell line NCI-H345, VIP increased the secretion rate of bombesin-like peptides about 3-fold.
  • In NCI-H345 cells, VIP raised cyclic AMP about 10-fold, from 2.0 to 21.2 pmol/mg protein.
  • Somatostatin (100 nM) alone did not change secretion but reversed the VIP-induced increase.
  • In one patient with extensive SCLC, plasma bombesin-like peptides rose about 10-fold to 500 pM after secretin infusion. Similar results were seen in one other patient with extensive disease, but not in three patients with limited SCLC or one patient with adenocarcinoma.
  • Bombesin immunoreactivity was found in the spinal fluid of 7 of 9 SCLC patients with meningeal carcinomatosis, 4 of 18 with parenchymal metastases and 1 of 15 controls.
  • Labeled [Tyr4]bombesin bound with high affinity (Kd = 0.5 nM) to a single class of about 1,500 sites per cell on NCI-H345.
  • The putative bombesin receptor antagonist (a substance P analog) had no effect on cytosolic calcium by itself but antagonized the response to 100 nM bombesin.
• The authors' conclusion: The authors concluded that SCLC cells have functional VIP receptors that regulate bombesin-like peptide secretion, and that bombesin receptor antagonists may serve as useful agents to inhibit the growth of SCLC.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Small Cell Lung Cancer, Adenocarcinoma, Carcinoma, Squamous Cell Carcinoma, Mesothelioma.

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