Author of

• 11481

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  P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11490

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    P2.02-009 - Expression of a splicing variant of the CADM1 specific to small cell lung cancer (ID 1832)

    11:46 - 12:03  |  Author(s): T. Ito
    • Abstract

    Background
    CADM1, a member of the immunoglobulin superfamily cell adhesion molecules, acts as a tumor suppressor in a variety of human cancers. CADM1 expression is frequently lost in various cancers and CADM1 inactivation by promoter methylation was observed in 44% of non-small cell lung cancer (NSCLC). In contrast, CADM1 is ectopically expressed in adult T-cell leukemia (ATL), conferring an invasive phenotype characteristic to ATL. Therefore, CADM1 plays dual roles in human oncogenesis: as a tumor suppressor in epithelial cancers and as an oncoprotein that promotes invasion in ATL cells. Here, we investigate the roles of CADM1 in small cell lung cancer (SCLC).

    Methods
    We studied splicing variant of CADM1 in 5 primary NSCLC tumors and a primary SCLC tumor, as well as 16 SCLC and 10 NSCLC cell lines. Expresssion and splicing variant of CADM1 was examined by RT-PCR, Western blotting, immunohistochemistry, and SSCP, respectively.

    Results
    Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM1 protein. Western blotting and RT-PCR analyses have revealed 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. Then, 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, a SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL.

    Conclusion
    CADM1 could provide a novel molecular target for the diagnosis and growth suppression of SCLC cells.