Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells

Int J Cancer. 1996 Sep 27;68(1):84-92. doi: 10.1002/(SICI)1097-0215(19960927)68:1<84::AID-IJC15>3.0.CO;2-6.


The 5T4 antigen is defined by a monoclonal antibody (MAb) specific for human trophoblast. It is also expressed by many types of tumour cell and has been associated with metastasis and poor clinical outcome in a number of cancers. This pattern of expression is consistent with a mechanistic involvement of 5T4 molecules in the spread of cancer cells. The 5T4 antigen is a transmembrane glycoprotein with a 310 amino acid extracellular domain and a 44 amino acid cytoplasmic domain. Transfection of full-length 5T4 cDNA into epithelial cells alters cell-cell contacts and cellular motility. Thus, in 5T4-transfected CL-S1 murine mammary cells, 5T4 expression is associated with dendritic morphology, accompanied by abrogation of actin/cadherin-containing contacts and increased motility. In transfected MDCK canine kidney epithelial cells, 5T4 over-expression also results in increased motility, but disruption of cell-cell contacts, either by culturing cells in low calcium medium or by addition of HGF/SF, is needed. The effects of 5T4 expression on morphology and motility are separable since cells transfected with a truncated form of 5T4 cDNA in which the cytoplasmic domain is deleted reveal that the latter is necessary to abrogate actin/cadherin-containing contacts but does not influence the effects on motility. Thus, 5T4 molecules can deliver signals through both the extracellular and intracellular domains, and the resultant effects are consistent with a role for 5T4 molecules in invasion processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Blotting, Western
  • Cell Communication*
  • Cell Line
  • Cell Movement*
  • Cytoskeleton / ultrastructure
  • Dogs
  • Epithelium / ultrastructure
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Kidney
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis*
  • Transfection


  • Antigens, Neoplasm
  • Membrane Glycoproteins
  • trophoblastic glycoprotein 5T4, human