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Tetanus toxin as a marker for small-cell lung cancer cell lines

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

Tetanus toxin labeling of human lung cancer cell lines was investigated using direct and indirect immunofluorescence and immunohistochemical staining. Cells of characterized permanent cell lines, eight small-cell lung cancer (SCLC) cell lines of classic subtype, six SCLC cell lines of variant subtype and seven non-small-cell lung cancer (NSCLC) cell lines, were incubated with a saturating concentration of tetanus toxin. For staining, fluorescein-isothiocyanate-(FITC)-conjugated anti-(tetanus toxin) antibodies were used or a mouse monoclonal anti-(fragment C) antibody with subsequent binding of FITC-conjugated anti-(mouse Ig) antibody or peroxidase-antiperoxidase complex. Only SCLC showed an intense fluorescence/immunoreactivity restricted to the cell membrane. Quantitative analysis of tetanus toxin labeling by flow cytometry revealed the percentage of positive cells to be between 35% and 95% in SCLC without obvious differences between the classic and variant subtypes of SCLC. In NSCLC the percentage of positive cells was lower than 10%. These results demonstrate that SCLC in contrast to NSCLC can be labeled with tetanus toxin, emphasizing the neuroendocrine properties of this tumor, and that tetanus toxin labeling may become a useful diagnostic marker for SCLC cells in cytology.

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Abbreviations

SCLC:

small-cell lung cancer

NSCLC:

non-small-cell lung cancer

FITC:

fluorescein-isothiocyanate

PBS:

phosphate-buffered saline

FACS:

fluorescence-activated cell sorter

NB:

neuroblastoma

APUD:

amine precursor uptake and decarboxylation

Fuc-GM1:

fucosylated GM1

Fuc-GD1b:

fucosylated GD1b (ganglioside nomenclature according to Svennerholm 1977)

References

  • Bepler G, Jaques G, Koehler A, Gropp C, Havemann K (1987a) Markers and characteristics of human SCLC cell lines. J Cancer Res Clin Oncol 113:253–259

    Google Scholar 

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

    Google Scholar 

  • Bepler G, Koehler A, Kiefer P, Havemann K, Beisenherz K, Jaques G, Gropp C, Haeder M (1988) Characterization of the state of differentiation of six newly established human non-small cell lung cancer cell lines. Differentiation 37:158–171

    Google Scholar 

  • Berliner P, Unsicker K (1985) Tetanus toxin labeling as a novel rapid and highly specific tool in human neuroblastoma differential diagnosis. Cancer 56:419–423

    Google Scholar 

  • Berliner P, Lietzke R, Unsicker K (1984) Binding of tetanus toxin to human neuroblastoma (NB) cells and NB cell lines. Verh Anat Ges 78:149–150

    Google Scholar 

  • Bunn Jr PA, Linnoila I, Minna JD, Carney D, Gazdar AF (1985) Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic diterminant present on natural killer cells. Blood 65:764–768

    Google Scholar 

  • Carney DN, Gazdar AF, Nau M, Minna JD (1985a) Biological heterogeneity of small cell lung cancer. Semin Oncol 12:289–303

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Critchley DR, Habig WH, Fishman PH (1986) Reevaluation of the role of gangliosides as receptors for tetanus toxin. J Neurochem 47:213–222

    Google Scholar 

  • Dimpfel W, Neale JH, Habermann E (1975) 125I-labelled tetanus toxin as a neuronal marker in tissue cultures derived from embryonic CNS. Naunyn-Schmiedeberg's Arch Exp Pathol Pharmakol 290:329–333

    Google Scholar 

  • Dimpfel W, Huang RTC, Habermann E (1977) Gangliosides in nervous tissue cultures and binding of 125I-labelled tetanus toxin, a neuronal marker. J Neurochem 29:329–334

    Google Scholar 

  • Eisenbarth GS, Shimizu K, Bowring MA, Wells S (1982) Expression of receptors for tetanus toxin and monoclonal antibody A2B5 by pancreatic islet cells. Proc Natl Acad Sci USA 79:5066–5070

    Google Scholar 

  • Fields KL, Brockers JP, Mirsky R, Wendon LMB (1978) Cell surface markers for distinguishing different types of rat dorsal root ganglion cells in culture. Cell 14:43–51

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Hanqing M, Avrova N, Mansson JE, Molin K, Svennerholm L (1986) Gangliosides and neutral glycosphingolipids of normal tissue and oat cell carcinoma of human lung. Biochim Biophys Acta 878:360–370

    Google Scholar 

  • Heitz PU (1987) neuroendocrine tumor markers. Curr Top Pathol 77:279–306

    Google Scholar 

  • Helting ThB, Zwisler O (1977) Structure of tetanus toxin. J Biol Chem 252:187–193

    Google Scholar 

  • Mirsky R (1982) The use of antibodies to define and study major cell types in the central and peripheral nervous system. In: Brookes J (ed) Neuroimmunology. Plenum Press, New York, pp 141–181

    Google Scholar 

  • Nilsson O, Mansson JE, Brezicka FT, Holmgren J, Lindholm L, Sörenson S, Yngvason F, Svennerholm L (1984) Fucosyl-GM1: a ganglioside associated with small cell lung carcinomas. Glycoconjugate J 1:43–49

    Google Scholar 

  • Nilsson O, Brezicka FT, Holungren J, Sörenson S, Svennerholm L, Yngvason F, Lindholm L (1986) Detection of a ganglioside antigen associated with small cell lung carcinomas using monoclonal antibodies directed againt fucosyl-GM1. Cancer Res 46:1403–1407

    Google Scholar 

  • Notter MFD, Leary JF (1985) Flow cytometric analysis of tetanus toxin binding to neuroblastoma cells. J Cell Physiol 125:476–484

    Google Scholar 

  • Pearse AGE (1969) The cytochemistry and ultrastructure of polypeptide hormone producing cells of the APUD series, and the embryologic, physiologic and pathologic implication of the concept. J Histochem Cytochem 17:303–313

    Google Scholar 

  • Pettengill OS, Sorenson GD, Wurster-Hill DH, Curphy 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

    Google Scholar 

  • Robinson JP, Hash JH (1982) A review of the molecular structure of tetanus toxin. Mol Cell Biochem 48:33–44

    Google Scholar 

  • Svennerholm L (1977) The nomenclature of lipids. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Eur J Biochem 79:11–21

    Google Scholar 

  • Tischler AS, Mobtaker H, Mann K, Nunnemacher G, Jason WJ, Dayal Y, de Lellis R, Adelman L, Wolfe HJ (1986) Anti-lymphocyte antibody Leu-7 (HNK-1) recognizes a constituent of neuroendocrine granule matrix. J Histochem Cytochem 34:1213–1216

    Google Scholar 

  • Van Heyningen WE (1974) Gangliosides as membrane receptors for tetanus toxin, cholera toxin and serotonin. Nature 249:415–417

    Google Scholar 

  • Watanabe J, Okabe T, Fujisawa M, Takaku F, Hirohashi S, Shimosato Y (1987a) Monoclonal antibody that distinguishes small cell lung cancer from non-small cell lung cancer. Cancer Res 47:826–829

    Google Scholar 

  • Watanabe J, Okabe T, Fujisawa M, Takaku F, Fukayama M (1987b) Isolation of small cell lung cancer-associated antigen from human brain. Cancer Res 47:960–962

    Google Scholar 

  • Yavin E (1984) Gangliosides mediate association of tetanus toxin with neural cells in culture. Arch Biochem Biophys 230:129–137

    Google Scholar 

  • Yavin E, Yavin Z, Habig WH, Hardegree MC, Kohn LD (1981) Tetanus toxin association with developing neuronal cell cultures. J Biol Chem 256:7014–7022

    Google Scholar 

  • Zamboni L, DeMartino L (1961) Buffered picric acid-formaldehyde: A new rapid fixative for electron microscopy. J Cell Biol 35:148A

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology/Oncology/Immunology, Philipps-University Marburg, Federal Republic of Germany

    Jochen Heymanns & Klaus Havemann

  2. Department of Pathology, Philipps-University Marburg, Federal Republic of Germany

    Kurt Neumann

Authors
  1. Jochen Heymanns
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  2. Kurt Neumann
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  3. Klaus Havemann
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Heymanns, J., Neumann, K. & Havemann, K. Tetanus toxin as a marker for small-cell lung cancer cell lines. J Cancer Res Clin Oncol 115, 537–542 (1989). https://doi.org/10.1007/BF00391354

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  • DOI: https://doi.org/10.1007/BF00391354

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