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CD24, a Signal-transducing Molecule Expressed on Human B Cells, Is a Major Surface Antigen on Small Cell Lung Carcinomas¹

Molecular Immunology Group, John Radcliffe Hospital, Oxford, UK [D. J., J. B.], and Department of Medicine, Division of Oncology, University Hospital, Zürich, Switzerland [R. W., E. W., R. A. S.]

Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining.

Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.

¹ This research was supported by the Swiss Cancer League (FOR.302.89.2) and by the Wellcome Trust.

² To whom requests for reprints should be addressed, at Molecular Immunology Group, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.

Received 3/23/92. Accepted 7/16/92.

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