Skip to main content
SpringerLink
Log in

Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-α were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3–30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

SCLC:

small cell lung cancer

ACTH:

adrenocorticotropic hormone

AVP:

arginine-vasopressin

CGRP:

calcitonin gene related peptide

GHRF:

growth hormone releasing factor

GRP:

gastrin releasing peptide

VIP:

vasoactive intestinal peptide

EGF:

epidermal growth factor

TGF:

transforming growth factor

CNTF:

ciliary neuronotrophic factor

NGF:

nerve growth factor

References

  • Allen AE, Carney DN, Moody TW (1988) Neurotensin binds with high affinity to small cell lung cancer cells. Peptides (in press)

  • Barbin G, Manthorpe M, Varon S (1984) Purification of the chick eye ciliary neuronotrophic factor. J Neurochem 43:1468–1478

    PubMed  Google Scholar 

  • Basset P, Zwiller J, Revel MO, Vincendon G (1985) Growth promotion of transformed cells by iron in serum-free culture. Carcinogenesis 6:355–359

    PubMed  Google Scholar 

  • Baylin SB, Weisburger WR, Eggleston JC, Mendelsohn G, Beaven MA, Abeloff MD, Ettinger DS (1978) Variable content of histaminase, l-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung: biologic and clinical implications. N Engl J Med 299:105–110

    PubMed  Google Scholar 

  • Bensch KG, Corrin B, Pariente R, Spencer H (1968) Oat cell carcinoma of the lung. Its origin and relationship to bronchial carcinoids. Cancer 22:1163–1172

    PubMed  Google Scholar 

  • Bepler G, Jaques G, Neumann K, Aumueller G, Gropp C, Havemann K (1987a) Establishment growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol 113:31–40

    PubMed  Google Scholar 

  • Bepler G, Jaques G, Havemann K, Koehler A, Johnson BE, Gazdar AF (1987b) Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer. Cancer Res 47:1883–1891

    PubMed  Google Scholar 

  • Bepler G, Carney DN, Gazdar AF, Minna JD (1987c) In vitro growth inhibition of human small cell lung cancer by physalaemin. Cancer Res 47:2371–2375

    PubMed  Google Scholar 

  • Bepler G, Jaques G, Koehler A, Gropp C, Havemann K (1987d) Neuroendocrine markers, classical tumor markers, and chromosomal characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol 113:253–259

    PubMed  Google Scholar 

  • Blobel GA, Gould VE, Moll R, Lee I, Huszar M, Geiger B, Franke WW (1985) Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms. Lab Intest 52:39–51

    Google Scholar 

  • Borland K, Mita M, Oppenheimer CL, Blinderman LA, Massague J, Hall PF, Czech MP (1984) The actions of insulin-like growth factors I and II on cultured Sertoli cells. Endocrinology 114:240–249

    PubMed  Google Scholar 

  • Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45:2913–2923

    PubMed  Google Scholar 

  • Carney DN, Cuttitta FC, Moody TW, Minna JD (1987) Selective stimulation of small cell lung cancer clonal growth by bombesin and gastrin-releasing peptide. Cancer Res 47:821–825

    PubMed  Google Scholar 

  • Cate CC, Pettengill OS, Sorenson GD (1986) Biosynthesis of procalcitonin in small cell carcinoma of the lung. Cancer Res 46:812–818

    PubMed  Google Scholar 

  • Chen TR (1977) In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res 104:255–262

    PubMed  Google Scholar 

  • Cuttitta F, Carney DN, Mulshine J, Moody TW, Fedorko J, Fischler A, Minna JD (1985) Bombesin-like peptides can function as autocrine growth factors in human small cell lung cancer. Nature 316:823–826

    PubMed  Google Scholar 

  • Darfler FJ, Insel PA (1983) Clonal growth of lymphoid cells in serum-free media requires elimination of H2O2 toxicity. J Cell Physiol 15:31–36

    Google Scholar 

  • Ekblom P, Thesleff I, Saxen L, Miettinen A, Timpl R (1983) Transferrin as a fetal growth factor: acquisition of responsiveness related to embryonic induction. Proc Natl Acad Sci USA 80:2651–2655

    PubMed  Google Scholar 

  • Findlay DM, DeLuise M, Michelangeli VP, Ellison M, Martin TJ (1980) Properties of a calcitonin receptor and adenylate cyclase in BEN cells, a human cancer cell line. Cancer Res 40:1311–1317

    PubMed  Google Scholar 

  • Gazdar AF, Carney DN, Nau MM, Minna JD (1985a) 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

    PubMed  Google Scholar 

  • Gazdar AF, Carney DN, Becker KL, Deftos LJ, Liang V, Go V, Marangos PJ, Moody TW, Wolfsen AR, Zweig MH (1985b) Expression of peptide and other markers in lung cancer cell lines. Recent Results Cancer Res 99:167–174

    PubMed  Google Scholar 

  • Goedert M, Reeve JG, Emson PC, Bleehen NM (1984) Neurotensin in human small cell lung carcinoma. Br J Cancer 50:179–183

    PubMed  Google Scholar 

  • Haeder M, Rotsch M, Bepler G, Hennig C, Havemann K, Heimann B, Moelling K (1988) EGF receptor in human non-small cell and small cell lung cancer cell lines. Cancer Res (in press)

  • Halton DM, Peterson WD, Hukku B (1983) Cell culture quality control by rapid isoenzymatic characterization. In Vitro 19:16–24

    PubMed  Google Scholar 

  • Huff KK, Kaufman D, Gabbay KH, Spencer EM, Lippman ME, Dickson RB (1986) Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res 46:4613–4619

    PubMed  Google Scholar 

  • Jensen RT, Jones SW, Folkers K, Gardner JD (1984) A synthetic peptide that is a bombesin receptor antagonist. Nature 309:61–63

    PubMed  Google Scholar 

  • Kiefer PE, Bepler G, Kubasch M, Havemann K (1987) Amplification and expression of proto-oncogenes in human small cell lung cancer cell lines. Cancer Res 47:6236–6242

    PubMed  Google Scholar 

  • Korman LY, Carney DN, Citron ML, Moody TW (1986) Secretin/vasoactive intestinal peptide-stimulated secretion of bombesin/gastrin releasing peptide from human small cell carcinoma of the lung. Cancer Res 46:1214–1218

    PubMed  Google Scholar 

  • Luster W, Gropp C, Kern HF, Wahl R, Roeher HD, Havemann K (1985) Peptide hormone production in lung cancer cell lines of different histopathological types. Recent Results Cancer Res 99:117–129

    PubMed  Google Scholar 

  • Marquardt H, Hunkapiller MW, Hood LE, Twardzik DR, DeLarco JE, Stephenson JR, Todaro GJ (1983) Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci USA 80:4684–4688

    PubMed  Google Scholar 

  • Minuto F, Del Monte P, Barreca A, Fortini P, Cariola G, Catrambone G, Giordano G (1986) Evidence for an increased somatomedin-C/insulin-like growth factor I content in primary human lung tumors. Cancer Res 46:985–988

    PubMed  Google Scholar 

  • Moody TW (1988) Small cell lung cancer neuropeptide receptors. Lung Cancer (in press)

  • Moody TW, Bertness V, Carney DN (1983) Bombesin-like peptides and receptors in human tumor cell lines. Peptides 4:683–686

    Article  PubMed  Google Scholar 

  • Moody TW, Carney DN, Korman LY, Gazdar AF, Minna JD (1985) Neurotensin is produced by and secreted from classic small cell lung cancer cells. Life Sci 36:1727–1732

    Article  PubMed  Google Scholar 

  • Mountjoy KG, Holdaway IM, Finlay GJ (1983) Insulin receptor regulation in cultured human tumor cells. Cancer Res 43:4537–4542

    PubMed  Google Scholar 

  • Nakanishi Y, Mulshine JL, Kasprzyk PG, Avis I, Treston AM, Gazdar AF, Cuttitta F (1988) Insulin-like growth factor-I can stimulate the proliferation of human small lung cancer cell lines. J. Endocrinol Metabol (in press)

  • Ng KW, Livesey SA, Larkins RG, Martin TJ (1983) Calcitonin effects on growth and on selective activation of type II isoenzyme of cyclic adenosine 3′,5′-monophosphate-dependent protein kinase in T47D human breast cancer cells. Cancer Res 43:794–800

    PubMed  Google Scholar 

  • Pettengill OS, Sorenson GD, Wurster-Hill DH, Curphey TJ, Noll WW, Cate CC, Maurer LH (1980) Isolation and growth characteristics of continuous cell lines from small-cell carcinoma of the lung. Cancer 45:906–918

    PubMed  Google Scholar 

  • Riley JH, Edbrooke MR, Craig RK (1986) Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma cell line reflects aberrant proteolytic processing. FEBS Lett 198:71–79

    Article  PubMed  Google Scholar 

  • Roth KA, Barchas JD (1986) Small cell carcinoma cell lines contain opioid peptides and receptors. Cancer 57:769–773

    PubMed  Google Scholar 

  • Said SI (1986) Vasoactive intestinal peptide. J Endocrinol Invest 9:191–200

    PubMed  Google Scholar 

  • Shaffer MM, Carney DN, Korman LY, Lebovic GS, Moody TW (1987) High affinity binding of VIP to human lung cancer cell lines. Peptides 8:1101–1106

    Article  PubMed  Google Scholar 

  • Sherwin SA, Minna JD, Gazdar AF, Todaro GJ (1981) Expression of epidermal and nerve growth factor receptors and soft agar growth factor production by human lung cancer cells. Cancer Res 41:3538–3542

    PubMed  Google Scholar 

  • Simms E, Gazdar AF, Abrams PG, Minna JD (1980) Growth of human small cell (oat cell) carcinoma of the lung in serum-free growth factor-supplemented medium. Cancer Res 40:4356–4363

    PubMed  Google Scholar 

  • Sorenson GD, Pettengill OS, Brinck-Johnson T, Cate CC, Maurer LH (1981) Hormone production by cultures of small cell carcinoma of the lung. Cancer 47:1289–1296

    PubMed  Google Scholar 

  • Sporn MB, Roberts AB (1985) Autocrine growth factors and cancer. Nature 313:745–747

    PubMed  Google Scholar 

  • Taetle R, Castagnola J, Mendelsohn J (1986) Mechanisms of growth inhibition by receptor monoclonal antibodies. Cancer Res 46:1759–1763

    PubMed  Google Scholar 

  • Todaro GJ, DeLarco JE (1978) Growth factors produced by sarcoma virus-transformed cells. Cancer Res 38:4147–4154

    PubMed  Google Scholar 

  • Weber S, Zuckerman JE, Bostwick DG, Bensch KG, Sikic BJ, Raffin TA (1985) Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma in vitro. J Clin Invest 75:306–309

    PubMed  Google Scholar 

  • Yoder DG, Moody TW (1987) High affinity binding of cholecystokinin to small cell lung cancer cells. Peptides 8:103–107

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine Division of Hematology and Oncology, Philipps University Medical Center, D-3550, Marburg, Federal Republic of Germany

    Gerold Bepler, Martin Rotsch, Gabriele Jaques, Maria Haeder, Jochen Heymanns, Gisela Hartogh, Paul Kiefer & Klaus Havemann

Authors
  1. Gerold Bepler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Rotsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriele Jaques
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Haeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jochen Heymanns
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gisela Hartogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Kiefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Klaus Havemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by the SFB 215 of the German Research Community

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bepler, G., Rotsch, M., Jaques, G. et al. Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. J Cancer Res Clin Oncol 114, 235–244 (1988). https://doi.org/10.1007/BF00405828

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00405828

Key words

Search

Navigation