Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies

S. T. Rosen, J. L. Mulshine, F. Cuttitta, J. Fedorko, D. N. Carney, A. F. Gazdar, J. D. Minna

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Abstract

The antigen expression of human small cell lung cancer (SCLC) was studied using a panel of 21 independent rat monoclonal antibodies. The panel was selected by isolating hybridomas producing antibodies reactive with two SCLC lines but not with autologous B-lymphoblastoid lines. The antibodies were then tested in radiobinding assays against a panel of 17 SCLC lines, 13 non-small cell lung cancer lines, 6 SCLC necropsy specimens, 13 neuroectodermal lines (melanomas, neuroblastomas, glioblastomas), 15 other human lines, the glycolipid extracts of SCLC, human meconium, and human red blood cells. Using immunohistochemical assays, 14 of the antibodies were tested against normal lung, liver, and kidney, and lung cancer biopsies and xenografts. These analyses revealed the following: (a) SCLC elicited predominantly immunoglobulin M antibodies despite hyperimmunization; (b) the 21 antibodies displayed distinct binding and immunohistochemical phenotypes, indicating that they recognized many different epitopes; (c) 14 of the 21 antibodies reacted with glycolipid determinants; (d) the 21 determinants were expressed on over 80% of SCLC cell lines, necropsy samples, and xenografts; (e) the determinants were also expressed on normal adult bronchial epithelium, proximal tubules of adult kidney, and in a few instances on other normal cell types; (f) the antigens were expressed less frequently on non-small cell lung cancer samples but did not clearly distinguish SCLC from non-small cell lung cancer; (g) biochemical and morphological variants of SCLC exhibiting more malignant and undifferentiated behavior and containing greatly amplified c-myc oncogenes failed to express several determinants or expressed them at lower levels; (h) and finally, while many human cell lines failed to express the antigens including human melanoma and glioblastoma lines, human neuroblastoma lines frequently did express the SCLC antigens. These detailed studies utilizing a panel of distinct monoclonal antibodies define a series of antigens on the surface of the majority of SCLC undescribed previously.

Original languageEnglish (US)
Pages (from-to)2052-2061
Number of pages10
JournalCancer Research
Volume44
Issue number5
StatePublished - 1984

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Differentiation Antigens
Small Cell Lung Carcinoma
Monoclonal Antibodies
Antibodies
Non-Small Cell Lung Carcinoma
Antigens
Glycolipids
Glioblastoma
Neuroblastoma
Heterografts
Melanoma
Cell Line
Meconium
Proximal Kidney Tubule
myc Genes
Kidney Neoplasms
Hybridomas
Surface Antigens
Liver Neoplasms
Immunoglobulin M

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rosen, S. T., Mulshine, J. L., Cuttitta, F., Fedorko, J., Carney, D. N., Gazdar, A. F., & Minna, J. D. (1984). Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies. Cancer Research, 44(5), 2052-2061.

Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies. / Rosen, S. T.; Mulshine, J. L.; Cuttitta, F.; Fedorko, J.; Carney, D. N.; Gazdar, A. F.; Minna, J. D.

In: Cancer Research, Vol. 44, No. 5, 1984, p. 2052-2061.

Research output: Contribution to journalArticle

Rosen, ST, Mulshine, JL, Cuttitta, F, Fedorko, J, Carney, DN, Gazdar, AF & Minna, JD 1984, 'Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies', Cancer Research, vol. 44, no. 5, pp. 2052-2061.
Rosen ST, Mulshine JL, Cuttitta F, Fedorko J, Carney DN, Gazdar AF et al. Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies. Cancer Research. 1984;44(5):2052-2061.
Rosen, S. T. ; Mulshine, J. L. ; Cuttitta, F. ; Fedorko, J. ; Carney, D. N. ; Gazdar, A. F. ; Minna, J. D. / Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies. In: Cancer Research. 1984 ; Vol. 44, No. 5. pp. 2052-2061.
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