title: Expression of a splicing variant of the  CADM1  specific to small cell lung cancer.
abstract: CADM1, a member of the immunoglobulin superfamily cell adhesion molecule, acts as a tumor suppressor in a variety of human cancers. CADM1 is also ectopically expressed in adult T-cell leukemia (ATL), conferring an invasive phenotype characteristic to ATL. Therefore, CADM1 plays dual roles in human oncogenesis. Here, we investigate the roles of CADM1 in small cell lung cancer (SCLC). Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM1 protein. Western blotting and RT-PCR analyses reveal that CADM1 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 CADM1 is involved in anchorage-independent growth in SCLC. In the present study, we demonstrate that SCLC expresses a unique splicing variant of CADM1 (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 CADM1 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 CADM1 show enhanced tumorigenicity in nude mice when transfected into SBC5, a SCLC cell lacking CADM1. Inversely, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of NCI-H69, an SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL, and could provide a molecular marker specific to SCLC.
authors.affiliation: Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Miwako
authors.initials: M
authors.lastname: Iwai
authors.forename: Mika
authors.initials: M
authors.lastname: Sakurai-Yageta
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maruyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Masataka
authors.initials: M
authors.lastname: Onizuka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins