Bombesin/Gastrin-Releasing Peptide Stimulation of Small-Cell Lung Cancer Clonal Growth

  • Desmond N. Carney
  • Terry W. Moody
  • Frank Cuttitta
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Small-cell lung cancer (SCLC) accounts for 20-25% of all new cases of primary lung cancer. Unlike the other major histological subtypes of lung cancer (collectively referred to as non-SCLC), SCLC is highly sensitive to both chemotherapy and radiation therapy. With combination chemotherapy a clinical response will be observed in up to 95% of all patients, and complete disappearance of all known tumor is seen in 40-50% of patients (Morstyn et al., 1984). However, in spite of the early dramatic responses observed in most patients, the vast majority will relapse with SCLC, and fewer than 10% of all patients will achieve long-term disease-free survival. The median survival for all patients is 10-11 months. Thus, there is a need to develop alternative approaches to the treatment of this tumor type.


Small Cell Lung Cancer Small Cell Carcinoma Clonal Growth Small Cell Lung Cancer Cell Continuous Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Carney, D. N., Bunn P. A., Gazdar, A. F., Pagan, J. A., and Minna, J. D., 1981a, Selective growth in serum-free hormone supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung, Proc. Natl. Acad. Sci. U.S.A. 78:3185–3189.PubMedCrossRefGoogle Scholar
  2. Carney, D. N., Gazdar, A. F., Bunn, P. A., and Guccion, J. G., 1981b, Demonstration of the stem cell nature of clonogenic cells in lung cancer specimens, Stem Cells 1:149–164.Google Scholar
  3. Carney, D. N., Oie, H., Moody, T. W., Gazdar, A. F., Cuttitta, F., and Minna, J. D., 1983, Bombesin stimulation of small cell lung cancer growth, Clin. Res. 31:404.Google Scholar
  4. Carney, D. N., Brower, M., Bertness, V., and Oie, H. K., 1984, The selective growth of human small cell lung cancer cell lines and clinical specimens in serum-free medium, in: Methods in Molecular and Cell Biology (G. Sato and D. Barnes, eds.), Alan R. Liss, New York, pp. 247–262.Google Scholar
  5. Carney, D. N., Gazdar, A. G., Bepler, G., Guccion, J., Moody, T. W., Marangos, P. J., Zweig, M. H., and Minna, J. D., 1985, Establishment and identification of small cell lung cancer cell lines having classic and variant features, Cancer Res. 45:2913–2923.PubMedGoogle Scholar
  6. Cuttitta, F., Carney, D. N., Mulshine, J., Moody, T. W., Fedorko, J., Fischler, A., and Minna, J., 1985, Bombesin-like peptides can function as autocrine growth factors in human small cell lung cancer, Nature 316:823–826.PubMedCrossRefGoogle Scholar
  7. Gazdar, A. F., Carney, D. N., Russel, E. K., Simms, H. L., Baylin, S. B., Bunn, P. A., Guccion, J. G., and Minna, J. D., 1980, Small cell carcinoma of the lung: Establishment of continuous clonable cell lines having APUD properties, Cancer Res. 40:3502–3507.PubMedGoogle Scholar
  8. Gazdar, A. F., Carney, D. N., Nau, M., and Minna, J. D., 1985, Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological and growth properties, Cancer Res. 45:2924–2930.PubMedGoogle Scholar
  9. Howlett, T. A., Price, J., Hale, A. C., Donlack, I., Rees, L. H., Wass, J. A. H., and Besser, G. M., 1985, Pituitary ACTH dependent Cushing’s syndrome due to ectopic production of a bombesin-like peptide by a medullary carcinoma of the thyroid, Clin. Endocrinol. 22:91–101.CrossRefGoogle Scholar
  10. Ihde, D. C., Makuch, R. W., Carney, D. N., Bunn, P. A., Cohen, M. H., Matthews, M. J., and Minna, J. D., 1981, Prognostic implications of stage of disease and sites of metastases in patients with small cell carcinoma of the lung treated with intensive chemotherapy, Am. Rev. Respir. Dis. 123:500–507.PubMedGoogle Scholar
  11. Jensen, R. T., Jones, S. W., Folkers, K., and Gardner, J. D., 1984, A synthetic peptide that is a bombesin receptor antagonist, Nature 309:61–63.PubMedCrossRefGoogle Scholar
  12. Little, C. D., Nau, M. M., Carney, D. N., Gazdar, A. F., and Minna, J. D., 1983, Amplification and expression of the C-myc oncogene in human lung cancer cell lines, Nature 306:194–196.PubMedCrossRefGoogle Scholar
  13. McDonald, T. G., Ghatei, M. A., Bloom, S. R., Adrian, T. E., Mochizuk, T., Yanaihara, C., and Yanihara, N., 1983, Dose response comparisons of canine plasma gastroenteropancreatic hormone response to bombesin and the porcine gastrin releasing peptide, Regul. Peptides 5:125–137.CrossRefGoogle Scholar
  14. Moody, T. W., Pert, C. B., Gazdar, A. F., Carney, D. N., and Minna, J. D., 1981, High levels of intracellular bombesin characterize human small cell lung cancer, Science 214:1246–1248.PubMedCrossRefGoogle Scholar
  15. Moody, T. W., Russell, E. K., O’Donohoe, T. L., Linden, C. D., and Gazdar, A. F., 1983a, Bombesin-like peptides in small cell lung cancer; biochemical characterization and secretion from a cell line, Life Sci. 32:487–493.PubMedCrossRefGoogle Scholar
  16. Moody, T. W., Bertness, V., and Carney, D. N., 1983b, Bombesin-like peptides and receptors in human tumours, Peptides 4:683–686.PubMedCrossRefGoogle Scholar
  17. Moody, T. W., Carney, D. N., Cuttitta, F., Quattrocchi, K., and Minna, J. D., 1985, High affinity receptors for bombesin/GRP-like peptides on human small cell lung cancer, Life Sci. 37: 105–113.PubMedCrossRefGoogle Scholar
  18. Morstyn, G., Ihde, D. C., Lichter, A. S., Bunn, P. A., Carney, D. N., Glatstein, E., and Minna, J. D., 1984, Small cell lung cancer 1973-1983: Early progress and recent obstacles, Int. J. Radiát. Oncol. 10:515–539.CrossRefGoogle Scholar
  19. Pandol, S. J., Jensen, R. T., and Gardner, J. D., 1982, Mechanism of [Tyr4bombesin-induced desen-sitization in dispersed acini from guinea pig pancreas, J. Biol. Chem. 20:12024–12029.Google Scholar
  20. Radice, P. A., Matthews, M. J., Ihde, D. C., Gazdar, A. F., Carney, D. N., Bunn, P. A., Cohen, M. H., Fossieck, B. E., Makuch, R. W., and Minna, J. D., 1982, The clinical behaviour of mixed small cell/large cell bronchogenic carcinoma compared to pure small cell subtypes, Cancer 50:2894–2902.PubMedCrossRefGoogle Scholar
  21. Rozengurt, E., and Sinnett-Smith, J., 1983, Bombesin stimulation of DNA synthesis and cell division in cultures of Swiss 3T3 cells, Proc. Natl. Acad. Sci. U.S.A. 80:2936–2940.PubMedCrossRefGoogle Scholar
  22. Weber, S., Zuckerman, J. E., Bostwick, D. G., Bensch, K. G., Sikic, B. I., and Raffin, T. A., 1985, Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma in vitro, J. Clin. Invest. 75:306–309.PubMedCrossRefGoogle Scholar
  23. Westendorf, J. M., and Schonbrunn, A., 1983, Characterization of bombesin receptors in a rat pituitary cell line, J. Biol. Chem. 258:7527–7535.PubMedGoogle Scholar
  24. Willey, J., Lechner, J. F., and Harris, C. C., 1984, Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells, Exp. Cell Res. 153:245–248.PubMedCrossRefGoogle Scholar
  25. Yamaguchi, K., Abe, K., Kameya, T., Actachi, I., Taguchi, S., Otsubo, K., and Yancuhara, N., 1983, Production and molecular size heterogeneity of immunoreactive gastrin releasing peptide in fetal and adult lungs and primary lung tumours, Cancer Res. 43:3932–3939.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Desmond N. Carney
    • 1
  • Terry W. Moody
    • 2
  • Frank Cuttitta
    • 3
  1. 1.Mater HospitalDublin 7Ireland
  2. 2.Department of BiochemistryThe George Washington University School of Medicine and Health SciencesUSA
  3. 3.NCI-Navy Medical Oncology BranchNational Naval Medical CenterBethesdaUSA

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