Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells

Nat Med. 1999 Mar;5(3):286-91. doi: 10.1038/6502.


As in the development of many human cancers, in a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2), expression of neural cell adhesion molecule (NCAM) changes from the 120-kDa isoform in normal tissue to the 140/180-kDa isoforms in tumors. NCAM-deficient RiplTag2 mice, generated by crossing Rip1Tag2 mice with NCAM knockout mice, develop metastases, a tumor stage that is not seen in normal Rip1Tag2 mice. In contrast, overexpression of NCAM 120 in NCAM-deficient Rip1Tag2 mice prevents tumor metastasis. The results indicate that the loss of NCAM-mediated cell adhesion is one rate-limiting step in the actual metastatic dissemination of beta tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Progression
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulinoma / genetics
  • Insulinoma / metabolism
  • Insulinoma / physiopathology*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Mesoderm
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Neural Cell Adhesion Molecules / genetics*
  • Neural Cell Adhesion Molecules / physiology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / physiopathology*
  • Protein Isoforms
  • Tumor Cells, Cultured


  • Neural Cell Adhesion Molecules
  • Protein Isoforms