Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212.
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 alpha-(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 alpha-(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 200,000-250,000, 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.
Moolenaar
C E
CE
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
Muller
E J
EJ
Schol
D J
DJ
Figdor
C G
CG
Bock
E
E
Bitter-Suermann
D
D
Michalides
R J
RJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008970:Molecular Weight; D009447:Neuroblastoma / Q000276:immunology*; D012795:Sialoglycoproteins / Q000032:analysis* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins