Expression of a splicing variant of the CADM1 specific to small cell lung cancer

CADM 1, a member of the immunoglobulin superfamily cell adhesion molecule, acts as a tumor suppressor in a variety of human cancers. CADM 1 is also ectopically expressed in adult T‐cell leukemia ( ATL ), conferring an invasive phenotype characteristic to ATL . Therefore, CADM 1 plays dual roles in human oncogenesis. Here, we investigate the roles of CADM 1 in small cell lung cancer ( SCLC ). Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM 1 protein. Western blotting and RT ‐ PCR analyses reveal that CADM 1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM 1 is involved in anchorage‐independent growth in SCLC . In the present study, we demonstrate that SCLC expresses a unique splicing variant of CADM 1 (variant 8/9) containing additional extracellular fragments corresponding to exon 9 in addition to variant 8, a common isoform in epithelia. Variant 8/9 of CADM 1 is almost exclusively observed in SCLC and testis, although this variant protein localizes along the membrane and shows similar cell aggregation activity to variant 8. Interestingly, both variant 8/9 and variant 8 of CADM 1 show enhanced tumorigenicity in nude mice when transfected into SBC 5, a SCLC cell lacking CADM 1. Inversely, suppression of CADM 1 expression by sh RNA reduced spheroid‐like cell aggregation of NCI ‐H69, an SCLC cell expressing a high amount of CADM 1. These findings suggest that CADM 1 enhances the malignant features of SCLC , as is observed in ATL , and could provide a molecular marker specific to SCLC . ( Cancer Sci 2012; 103: 1051–1057)