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Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines

  • Original Papers
  • Experimental Oncology
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Summary

Cell lines from SCLC were established with a success rate of 43% from different metastatic sites of treated and untreated patients. All 6 SCLC cell lines grew as floating cell aggregates without substrate adherence. The degree of aggregation ranged from very tight spheroids to very loose sheets and chains. This gross morphological property showed a striking correlation to the PDT, with short PDTs in loose growing cell lines and long PDTs in tight growing cell lines. Cell size and nuclear features, i.e., chromatin pattern and nucleolar prominence, also seemed to correlate with the PDT and gross morphology. All SCLC cell lines had dense core granules by electron microscopical examination. Several different serum-free and serum-supplemented growth media were tested for their feasibility in estabilishing and permanently growing SCLC. Serum-free SIT medium and SIT 2.5 medium provided the best results in liquid culture. For semisolid SCLC cultivation, R10 medium was suprior to all other media tested. These cell lines are currently under intensive biochemical, molecular biological, and cytogenetical investigation in different laboratories and thus provide a tool for studying the biology of lung cancer.

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Abbreviations

SCLC:

small cell lung cancer

FBS:

fetal bovine serum

R 10:

Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with 10% FBS

D 10:

Dulbecco's modified Eagle's medium supplemented with 10% FBS

SIT:

RPMI 1640 medium supplemented with selenium, insulin, transferrin

HITES:

RPMI 1640 medium supplemented with hydrocortisone, insulin, transferrin, estradiol, selenium

SIT 2.5:

SIT medium supplemented with 2.5% FBS

PBS:

phosphate buffered saline

PDT:

population doubling time

References

  • American Cancer Society (1986) Cancer Facts and Figures

  • andrews JL, Bloom S, Balogh K, Beamis JF (1985) Lung cancer in women. Lahey clinic experience. Cancer 55:2894–2898

    PubMed  Google Scholar 

  • Baillie-Johson H, Twentyman PR, Fox NE, Walls GA, Workman P, Watson JV, Johnson N, Reeve JG, Bleehen NM (1985) Establishment and characterization of cell carcinoma). Br J Cancer 52:495–504

    PubMed  Google Scholar 

  • Baylin SB, Abeloff MD, Goodwin G, Carney DN, Gazdar AF (1980) Activities of l-dopa decarboxylase and diamine oxidase (histaminase) in lung cancers and decarboxylase as a marker for small (oat) cell cancer in culture. Cancer Res 40:1990–1994

    PubMed  Google Scholar 

  • Bensch KG, Corrin B, Parunte 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, Rotsch M, Jaques G, Zeymer U, Havemann K (1986a) Neuroendocrine differentiation and growth control of human small cell lung cancer cell lines. Anticancer Res 6:396

    Google Scholar 

  • Bepler G, Carney DN, Nau MM, Gazda AF, Minna JD (1986b) Additive and differential biologic activity of α-interferon A, difluoromethylornithine, and their combination on established human lung cancer cell lines. Cancer Res 46:3412–3419

    Google Scholar 

  • Bergh J, Larsson E, Zech L, Nisson K (1982) Establishment and characterization of two neoplastic cell lines (U-1285 and U-1568) derived from small cell carcinoma of the lung. Acta Pathol Microbiol Immunol Scand Sect A 90:149–158

    Google Scholar 

  • Bergh J, Nilsson K, Ekman R, Giovanella B (1985) Establishment and characterization of cell lines from human small cell and large cell carcinomas of the lung. Acta Pathol Microbiol Immunol Scand Sect A 93:133–147

    Google Scholar 

  • Carney DN, Bunn PA, Gazdar AF, Pagan JA, Minna JD (1981) 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 USA 78:3185–3189

    PubMed  Google Scholar 

  • Carney DN, Mitchell JB, Kinsella TJ (1983) In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variant. Cancer Res 43:2806–2811

    PubMed  Google Scholar 

  • Carney DN, Gazdar AF, Bunn PA, Guccion JG (1984) Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells 1:149–164

    Google Scholar 

  • Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985a) 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, Bepler G, Gazdar AF (1985b) The serum-free establishment and in vitro growth properties of classic and variant small cell lung cancer cell lines. Recent Results Cancer Res 99:157–166

    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 

  • Editorial (1985) Lung cancer surpasses breast cancer as mortality risk to Texas women. Oncolog. 30:1

  • Fisher ER, Paulson JD (1978) A new in vitro cell line established from human large cell variant of oat cell lung cancer. Cancer Res 38:3830–3835

    PubMed  Google Scholar 

  • Gazdar AF, Carney DN, Russel EK, Sims HL, Baylin SB, Bunn PA, Guccion JG, Minna JD (1980) Establishment of continuous, clonable cultures of small-cell carcinoma of the lung which have amine precursor uptake and decarboxylation cell properties. Cancer Res 40:3502–3507

    PubMed  Google Scholar 

  • Gazdar AF, Zweig MH, Carney DN, Van Steirteghen AC, Baylin SB, Minna JD (1981) Levels of creatine kinase and its BB isoenzyme in lung cancer specimens and cultures. Cancer Res 41:2773–2777

    PubMed  Google Scholar 

  • Gazdar AF, Carney DN, Nau MM, Minna JD (1985) Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological and growth properties. Cancer Res 45:2925–2930

    Google Scholar 

  • Goodwin G, Baylin SB (1982) Relationships between neuroendocrine differentiation and sensitivity to gamma-radiation in culture line OH-1 of human small cell lung carcinoma. Cancer Res 42:1361–1367

    PubMed  Google Scholar 

  • Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463

    PubMed  Google Scholar 

  • Ito S, Karnovsky MJ (1968) Formaldehyde-glutaraldehyde fixatives containing trinitro compounds. J Cell Biol 39:168A-169A

    Google Scholar 

  • Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196

    PubMed  Google Scholar 

  • Marangos PJ, Gazdar AF, Carney DN (1982) Neuron specific enolase in human small cell carcinoma cultures. Cancer Lett 15:67–71

    Article  PubMed  Google Scholar 

  • Matthews MJ (1976) Problems in morphology and behavior of bronchopulmonary malignant disease. In: Israel L, Chahanion P (eds) Lung cancer, facts, problems and prospects. Academic Press, New York, pp 23–62

    Google Scholar 

  • Matthews MJ (1985) Pathology of small cell lung cancer. Clin Oncol 4:11–29

    Google Scholar 

  • Matthews MJ, Gazdar AF (1981) Pathology of small cell carcinoma of the lung and its subtypes. A clinico-pathologic correlation. In: Livingston RB (ed) Lung cancer. Martinus Nijhoff Publishers, The Hague Boston London, pp 283–306

    Google Scholar 

  • Meyskens FL, Thomson SP, Moon TE (1984) Quantitation of the number of cells within tumor clonies in semisolid medium and their growth as oblate spheroids. Cancer Res 44:271–277

    PubMed  Google Scholar 

  • Minna JD, Higgins GA, Glatstein EJ (1982) Cancer of the lung. In: DeVita VT, Hellman S, Rosenberg SA (eds) Principles and practice in oncology. Lippincott, Philadelphia, pp 396–473

    Google Scholar 

  • Moody TW, Pert CB, Gazdar AF, Carney DN, Minna JD (1981) High levels of intracellular bombesin characterize human small-cell lung carcinoma. Science 214:1246–1248

    PubMed  Google Scholar 

  • Oboshi S, Tsugawa S, Seido T, Shimosato Y, Koide T, Ishikawa S (1971) A new floating cell line derived from human pulmonary carcinoma of oat cell type. GANN 62:505–514

    PubMed  Google Scholar 

  • Ohara H, Okamoto T (1977) A new in vitro cell line established from human oat cell carcinoma of the lug. Cancer Res 73:3088–3095

    Google Scholar 

  • Olsson L, Sorenson HR, Behnke O (1984) Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies. Cancer 54:1757–1765

    PubMed  Google Scholar 

  • Pettengill OS, Faulkner CS, Wurster-Hill DH, Maurer LH, Sorenson GD, Robinson AG, Zimmerman EA (1977) Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung. J Natl Cancer Inst 58:511–518

    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 

  • Radice PA, Matthews MJ, Ihde DC, Gazdar AF, Carney DN, Bunn PA, Cohen MH, Fossieck BE, Makuch RW, Minna JD (1982) The clinical behavior of mixed small cell/large cell bronchogenic carcinoma compared to pure small cell subtypes. Cancer 50:2894–2902

    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 

  • Smyth JF, Hansen HH (1985) Current status of research into small cell carcinoma of the lung: Summary of the second workshop of the international association for the study of lung cancer. Eur J Cancer Clin Oncol 21:1295–1298

    Article  PubMed  Google Scholar 

  • Spiro SG (1985) Chemotherapy of small cell lung cancer. Clin Oncol 4:105–120

    Google Scholar 

  • Whang-Peng J, Kao-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AF, Minna JD (1982) Specific chromosome defect associated with human small-cell lung cancer: deletion 3p (14–23). Science 215:181–182

    PubMed  Google Scholar 

  • World Health Organization (1982) The world health organization histological typing of lung tumors, second edition. Am J Clin Pathol 77:123–136

    Google Scholar 

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This work was supported by the SFB 215 of the German Research Society. The authors Thank Dr. Adi F. Gazdar for reviewing the morphology

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Bepler, G., Jaques, G., Neumann, K. et al. Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol 113, 31–40 (1987). https://doi.org/10.1007/BF00389964

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  • DOI: https://doi.org/10.1007/BF00389964

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