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Two Novel Cell Surface Antigens on Small Cell Lung Carcinoma Defined by Mouse Monoclonal Antibodies NE-25 and PE-35¹

Departments of Thoracic Surgery [Ta. T., M. I., T. A.] and Biochemistry [T. N.], Nagoya University School of Medicine, Showa-ku, Nagoya 466; Laboratories of Chemotherapy and Immunology [R. U., X. S., K. N., To. T.] and Department of Internal Medicine [Y. A., K. O.], Aichi Cancer Center, Chikusa-ku, Nagoya 464; Institute for Comprehensive Medical Science [M. S.], Fujita-Gakuen Health University, Toyoake, Aichi 470-11; First Department of Pathology [R. N.], Aichi Medical University, Nagakute-cho, Aichi 480-11; and Department of Biochemistry [K. K.], Institute for Developmental Research, Aichi Prefectural Colony, Kasugai, Aichi 480-03, Japan

Two mouse monoclonal antibodies, NE-25 and PE-35, defining novel cell surface antigens of small cell lung carcinoma (SCLC) were produced. The molecular weight of NE-25 and PE-35 antigens estimated by radioimmunoprecipitation was 25,000 and 35,000, respectively.

NE-25 antigen was expressed on the majority of cell lines and tumor specimens of SCLC among lung carcinoma. These NE-25-positive cell lines showed typical growth morphology as SCLC classic lines and expressed high levels of neuroendocrine biomarkers, such as aromatic L-amino acid decarboxylase, while NE-25 antigen-negative lines lacked apparent neuroendocrine properties. This antigen was expressed also on a subset of neoplastic cells with (neuro)endocrine properties, including pulmonary carcinoid, and on various tumors of nervous tissues, such as neuroblastoma. Among the normal cells, Kulchitski cells of lung, thyroid gland, adrenal gland, Langerhans islet, and nervous tissues were positive. Thus, the expression of NE-25 antigen is closely associated with the neural and/or (neuro)endocrine differentiation state.

On the contrary, PE-35 antigen was present on four major types of lung carcinomas as well as on squamous cell carcinoma and adenocarcinomas of various tissues, but it was absent from nervous tissue tumors. Thus, PE-35 antibody showed a "pan-epithelial" reactivity.

Analysis by NE-25 and PE-35 antibodies provided evidence for the heterogeneities of SCLC by demonstrating four surface phenotypes, with the NE-25⁺/PE-35⁺ phenotype being most common. In addition, the results supported the current understanding that various histological types of lung carcinoma, including SCLC, are derived from a stem cell of the bronchial epithelium.

¹ This study was supported in part by a Grant-in-Aid for the Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health and Welfare; Grant-in-Aids for Cancer Research from the Ministries of Education, Science, and Culture and of Health and Welfare in Japan; and by a grant from the Cancer Research Institute, Inc., New York, NY.

² Present address: Department of Immunology, Cancer Institute, Harbin Medical College, Harbin, China.

³ To whom requests for reprints should be addressed.

Received 4/10/86. Accepted 5/23/86.

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