L1-CAM in cancerous tissues

Expert Opin Biol Ther. 2008 Nov;8(11):1749-57. doi: 10.1517/14712598.8.11.1749.

Abstract

Background: L1-cell adhesion molecule (L1-CAM) is a cell adhesion receptor of the immunoglobulin superfamily, known for its roles in nerve cell function. While originally believed to be present only in brain cells, in recent years L1-CAM has been detected in other tissues, and in a variety of cancer cells, including some common types of human cancer.

Objective/methods: We review the prevalence of L1-CAM in human cancer, the possible mechanisms involved in L1-CAM-mediated tumorigenesis, and cancer therapies based upon L1-CAM antibody treatment.

Results/conclusions: In colon cancer cells, the L1-CAM gene was identified as a target of the Wnt/beta-catenin-TCF signaling pathway, and L1-CAM was exclusively detected at the invasive front of colon and ovarian cancer tissue. The expression of L1-CAM in normal and cancer cells enhanced tumorigenesis and conferred metastasis in colon cancer cells. Antibodies against the L1-CAM ectodomain severely inhibited the proliferation of a variety of cancer cells in culture and reduced tumor burden when injected into mice harboring cancer cells expressing L1-CAM. These results, in addition to the presence of L1-CAM on the cell surface and its restricted distribution in normal tissues, make it an ideal target for tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Neoplasm Metastasis*
  • Neoplasms / metabolism*
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Neural Cell Adhesion Molecule L1 / physiology
  • Signal Transduction
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Neural Cell Adhesion Molecule L1
  • Wnt Proteins
  • beta Catenin
  • Extracellular Signal-Regulated MAP Kinases