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

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‐SI 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. © 1996 Wiley‐Liss, Inc.