Skip to main content
SpringerLink
Log in
Book cover

Effects of Nicotine on Biological Systems II pp 151–158Cite as

Mechanisms of Nicotine Stimulated Cell Proliferation in Normal and Neoplastic Neuroendocrine Lung Cells

  • Chapter

Part of the book series: Advances in Pharmacological Sciences ((APS))

Summary

The secretion of several growth factors by pulmonary neuro-endocrine (PNE) cells is under cholinergic control, and nicotine stimulates the proliferation of fetal PNE cells in vivo by binding to the nicotinic acetylcholine receptor (nAChR). Our data show that fetal hamster PNE cells and cell lines derived from human neuroendocrine lung cancers require simultaneous stimulation of the oxygen receptor and the nAChR expressed in these cells in order to proliferate in response to nicotine. The simultaneous stimulation of these two receptor-initiated signal transduction pathways triggers secretion of 5-HT and bombesin, and activates protein kinase C (PKC) and c-fos downstream. The importance of this synergism is greatly emphasized by our finding that simultaneous exposure of hamsters to hyperoxia and nicotine causes lung tumors positive for 5-HT and neuron specific enolase (NSE) while nicotine alone or hyperoxia alone cause no tumors.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Schuller HM.: Small cell cancer of the lung: The role of unphysiological pulmonary oxygen levels. Biochem Pharmacol 1988; 37: 1645–1649.

    Article  PubMed  CAS  Google Scholar 

  2. Lauweryns J., Cokelaer M., Lerut T., Theuninck P.: Cross circulation studies on the role of hypoxia and hypoxemia on neuroepithelial bodies in young rabbits. Cell Tiss Res 1978; 36: 767–773.

    Google Scholar 

  3. Youngson C, Nurse C, Yeger H, Cutz E.: Oxygen sensing in airway chemoreceptors. Nature 1993; 365: 153–155.

    Article  PubMed  CAS  Google Scholar 

  4. Weiss W.: COPD and lung cancer. In: Obstructive Pulmonary Disease. Cherniak ED, editor. Philadelphia: WB Saunders, 1991: 344–347.

    Google Scholar 

  5. Mulshine JL, Treston AM, Natale RB, Kasprzyk PG, Avis I, Nakanishi Y, Cuttitta F.: Autocrine growth factors as therapeutic targets in lung cancer. Chest 1989;96:31s-34s.

    Google Scholar 

  6. Rozengurth E, Sinnett-Smith J.: Bombesin stimulation of fibroblast mitogenesis: specific receptors, signal transduction, and early events. Philos Trans R Soc Lond Biol 1990; 327: 209–221.

    Article  Google Scholar 

  7. Cutz E, Gillan JE, Track NS.: Pulmonary endocrine cells in the developing human lung and during neonatal adaptation. In: The Endocrine Lung in Health and Disease. Becker KL, Gazdar AF, editors. Philadelphia: WB Saunders, 1984: 210–231.

    Google Scholar 

  8. Gazdar AF.: The biology of endocrine lung tumors. In: The Endocrine Lung in Health and Disease. Becker KL, Gazdar AF, editors. Philadelphia: WB Saunders, 1984: 448–459.

    Google Scholar 

  9. Schuller HM, Hegedus TJ.: Effects of endogeneous and tobacco-related amines and nitrosamines on cell growth and morphology of a cell line derived from a human neuroendocrine lung cancer. Toxicol In Vitro 1989; 3: 37–43.

    Article  PubMed  CAS  Google Scholar 

  10. Cattaneao MG, Codignola A, Vicenti LM, Clementi F, Sher E.: Nicotine stimulates a serotonergic autocrine loop in human small cell lung carcinoma. Cancer Res 1993; 53: 5566–5568.

    Google Scholar 

  11. Schuller HM.: Carbon dioxide potentiates the mitogenic effects of nicotine and its carcinogenic derivative NNK in normal and neoplastic neuroendocrine lung cells via stimulation of autocrine and protein kinase C-dependent mitogenic pathways. Neurotoxicol (in press).

    Google Scholar 

  12. Tabassian AR, Nylen ES, Giron AE, Snider RH, Cassidy MM, Becker KL.: Evidence for cigarette smoke-induced calcitonin secretion from lungs of man and hamster. Life Sci 1988; 42: 2323–2329.

    Article  PubMed  CAS  Google Scholar 

  13. Nylen ES, Linnoila IR, Becker KL.: Prenatal cholinergic stimulation of pulmonary neuroendocrine cells by nicotine. Acta Physiol Scand 1988; 132: 117–118.

    Article  PubMed  CAS  Google Scholar 

  14. Reznik-Schuller HM.: Proliferation of endocrine (APUD-type) cells during early DEN-induced lung carcinogenesis. Cancer Lett 1976; 1: 255–258.

    Article  PubMed  CAS  Google Scholar 

  15. Linnoila IR, Becker KL, Silva OC, Snider RH, Moore CF.: Calcitonin as a marker for diethylnitrosamineinduced pulmonary endocrine cell hyperplasia in hamsters. Lab Invest 1984; 51: 39–45.

    PubMed  CAS  Google Scholar 

  16. Schuller HM, Witschi H-P, Nylen ES, Joshi PA, Correa E, Becker KL.: Pathobiology of NNK-induced lung tumors in hamsters and the modulating effect of hyperoxia. Cancer Res 1990; 50: 1960–1965.

    PubMed  CAS  Google Scholar 

  17. Schuller HM, Castonguay A, Orloff M, Rossignol G.: Modulation of the uptake and metabolism of 4(methylnitroamino)-1-(3-pyridyl)-1-butanone by nicotine in hamster lung. Cancer Res 1990; 50: 1960–1965.

    PubMed  CAS  Google Scholar 

  18. Schuller HM.: Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines. Biochem Pharmacol 1989; 38: 3439–3442.

    Article  PubMed  CAS  Google Scholar 

  19. Schuller HM, Nylen ES, Park P, Becker KL.: Nicotine, acetylcholine, and bombesin are trophic growth factors in neuroendocrine cell lines derived from experimental hamster lung tumors. Life Sci 1990; 47: 57 1578.

    Google Scholar 

  20. Maneckje R, Minna JD.: Opioid and nicotine affect growth regulation of human lung cancer cell lines. Proc Natl Acad Sci 1990; 87: 3294–3298.

    Article  Google Scholar 

  21. Linnoila IR, Funa K, Becker KL, Schuller HM, Gazdar AF.: Longterm selective culture of hamster pulmonary endocrine cells. Clin Res 1985; 33: 468A.

    Google Scholar 

  22. Schuller HM, Orloff M.: Carbon dioxide and oxygen stimulate proliferation of neuroendocrine lung cancer cell lines via protein kinase C activation. Proc Amer Assoc Cancer Res 1993; 34: 1049.

    Google Scholar 

  23. Miller MS, Schuller HM.: Nicotine stimulates the proliferation of fetal hamster pulmonary neuroendocrine cells. Proc Amer Assoc Cancer Res 1994; 35: 746.

    Google Scholar 

  24. Chan J, Patrick J, Quik M.: A role for the nicotinic a-bungarotoxin receptor in cell proliferation in small cell lung carcinoma. Soc Neurosci 1993; 19: 195–20.

    Google Scholar 

  25. Lamberdson O.: The atmosphere and gas exchanges with the lungs and blood. In: Medical Physiology. Mountcastle VB, editor. Saint Louis: CV Mosby Co, 1974: 1372–1398.

    Google Scholar 

  26. Schuller HM, McGavin D, Riechen A.: Nicotine induces tumors in hyperoxic hamstes. Proc Amer Assoc Cancer Res 1994; 35: 763.

    Google Scholar 

  27. Richter E, Tricker AR.: Nicotine inhibits the metabolic activation of the tobacco-specific nitrosamine 4(methylnitrosamino)-1-(3-pyridyl)-1-butanonein rats. Carcinogenesis 1994: 15: 1061–1064.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Carcinogenesis and Developmental Therapeutics Program, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, 37901, USA

    H. M. Schuller

Authors
  1. H. M. Schuller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, H3G 1Y6, Montreal, Québec, Canada

    Paul Brian Sydenham Clarke  & Maryka Quik  & 

  2. Stiftung für Verhalten und Umwelt, Pettenkoferstrasse 12, D-80336, München, Germany

    Franz Adlkofer (Sekretär) (Sekretär)

  3. Physiologisches Institut, Universität München, Pettenkoferstrasse 12, D-80336, München, Germany

    Klaus Thurau (Vorstand) (Vorstand)

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Birkhäuser Verlag Basel

About this chapter

Cite this chapter

Schuller, H.M. (1995). Mechanisms of Nicotine Stimulated Cell Proliferation in Normal and Neoplastic Neuroendocrine Lung Cells. In: Clarke, P.B.S., Quik, M., Adlkofer, F., Thurau, K. (eds) Effects of Nicotine on Biological Systems II. Advances in Pharmacological Sciences. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7445-8_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7445-8_19

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7447-2

  • Online ISBN: 978-3-0348-7445-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation