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

Shinji Kikuchi1, Miwako Iwai, Mika Sakurai-Yageta

  • 1Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Cancer Science
|March 21, 2012
PubMed

Insights

Cell adhesion molecule 1 (CADM1) has dual roles in cancer. In small cell lung cancer (SCLC), CADM1 expression enhances tumor growth and invasiveness, suggesting it could be a specific SCLC marker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member with known tumor suppressor roles.
  • CADM1 exhibits dual functions in oncogenesis, acting as a tumor suppressor in some cancers and promoting invasion in adult T-cell leukemia (ATL).

Purpose of the Study:

  • To investigate the specific roles of CADM1 in small cell lung cancer (SCLC).
  • To determine if CADM1 expression correlates with SCLC phenotypes and to identify potential CADM1 isoforms in SCLC.

Main Methods:

  • Immunohistochemistry to detect CADM1 protein in primary SCLC tumors.
  • Western blotting and RT-PCR to analyze CADM1 expression in SCLC cell lines with different growth characteristics.
  • Transfection and shRNA-mediated suppression to assess the functional impact of CADM1 variants on SCLC cell behavior and tumorigenicity.
  • Analysis of CADM1 splicing variants in SCLC.

Main Results:

  • CADM1 protein was expressed in 29% of primary SCLC tumors.
  • CADM1 expression was significantly higher in SCLC cells with anchorage-independent growth (suspension cultures) compared to attached cells.
  • A unique CADM1 splicing variant (variant 8/9) was identified in SCLC, also found in the testis.
  • Both CADM1 variant 8 and variant 8/9 enhanced tumorigenicity in SCLC cells lacking endogenous CADM1.
  • Suppression of CADM1 reduced spheroid-like aggregation in SCLC cells with high CADM1 expression.

Conclusions:

  • CADM1 plays a role in promoting malignant features of SCLC, including anchorage-independent growth and enhanced tumorigenicity.
  • The unique CADM1 variant 8/9 is predominantly found in SCLC.
  • CADM1 may serve as a specific molecular marker for SCLC, similar to its role in ATL.

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