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Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer

Nature volume 316, pages 823–826 (1985)Cite this article

Abstract

The autocrine hypothesis proposes that a cell produces and secretes a hormone-like substance that can interact with specific membrane receptors on its surface to induce effects such as proliferation1. Thus, a cancer cell could act to stimulate its own growth. Bombesin and bombesin-like peptides (BLPs) such as gastrin-releasing pep-tide (GRP) cause various physiological responses in mammals2, including stimulation of proliferation of 3T3 mouse fibroblasts3 and normal human bronchial epithelial cells in vitro4 and induction of gastrin cell hyperplasia and increased pancreatic DNA content in vivo in rats5,6. Human small-cell lung cancer (SCLC) cell lines produce and secrete BLPs7–12 and can express a single class of high-affinity receptors for BLPs13. Exogenously added BLPs can also stimulate the clonal growth and DNA synthesis of SCLC in vitro14,15. These findings suggest that BLPs function as autocrine growth factors for this tumour. One way to test this hypothesis is to interrupt the function of the endogenously produced BLPs. Here, we demonstrate that a monoclonal antibody to bombesin binds to the C-terminal region of BLPs, blocks the binding of the hormone to cellular receptors and inhibits the clonal growth of SCLC in vitro and the growth of SCLC xenografts in vivo. These results demonstrate that BLPs can function as autocrine growth factors for human SCLC.

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Author notes

  1. Terry W. Moody: Department of Biochemistry, George Washington University School of Medicine and Health Science, Washington, DC 20037, USA

Authors and Affiliations

  1. National Cancer Institute-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute and Naval Hospital, Bethesda, Maryland, 20814, USA

    Frank Cuttitta, Desmond N. Carney, James Mulshine, Terry W. Moody, Joseph Fedorko, Adam Fischler & John D. Minna

Authors
  1. Frank Cuttitta
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  2. Desmond N. Carney
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  3. James Mulshine
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  4. Terry W. Moody
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  5. Joseph Fedorko
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  6. Adam Fischler
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  7. John D. Minna
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Cuttitta, F., Carney, D., Mulshine, J. et al. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316, 823–826 (1985). https://doi.org/10.1038/316823a0

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