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Divisions of Tumor Biology [C. E. C. K. M., E. J. M., D. J. S., R. J. A. M. M.] and Immunology [C. G. F.], The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Protein Laboratory, University of Copenhagen, DK-2200 Copenhagen, Denmark [E. B.]; and Institute for Medical Microbiology, University of Hannover, Hannover, West Germany [D. B-S.]
Monoclonal antibodies (MAbs) 123C3 and 123A8 generated against a membrane preparation of a small cell lung carcinoma (SCLC) specimen recognize not only SCLC and bronchial carcinoids but also a significant portion of non-small cell lung carcinomas (non-SCLC) of various histological types. Together with 13 other monoclonal antibodies, which show preference for SCLC, they have been ranked as SCLC cluster 1 (SC-1) Mabs.
In this study we show that SC-1 MAbs are directed against a restricted number of epitopes, and that SC-1 MAbs and a polyclonal antiserum directed against the neural cell adhesion molecule (NCAM) recognize identical glycoproteins, indicating that SC-1 antigens are closely related to or identical with NCAM. Long polysialic acid units composed of
-(2,8)-linked N-acetylneuraminic acid units, which in mammals are found exclusively on NCAM, were present on SC-1 antigens in SCLC. This provides further evidence that SC-1 MAbs recognize NCAM. The SC-1 antigens in the SCLC cell line H69 were present in two forms, NCAM-containing
-(2,8)-polysialic acid units identified by antiserum 735, the NCAM-H form, and the less sialylated NCAM-L form. The NCAM-H form consisted of diffusely migrating sialoglycoproteins with a molecular weight of 200,000250,000, which resolved after neuraminidase treatment into two proteins with molecular weights of 140,000 and 180,000.
Since the NCAM-H form is expressed in the lung tumor type with a poor prognosis, our results suggest that NCAM might be implicated in the invasive behavior of these NCAM-positive lung tumors.
1 This study was partially supported by a grant from Centocor Europe BV, Leiden, The Netherlands.
2 Present address: Department of Obstetrics and Gynaecology; Free University Hospital, Amsterdam, The Netherlands.
3 To whom requests for reprints should be addressed.
Received 6/13/89. Revised 10/23/89. Accepted 10/30/89.
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