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-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.
CRC Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
C J
CJ
Carsberg
K A
KA
Myers
P L
PL
Stern
D000818:Animals; D000951:Antigens, Neoplasm; D015153:Blotting, Western; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000648:ultrastructure; D004285:Dogs; D004848:Epithelium / Q000648:ultrastructure; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D014162:Transfection
D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; C063709:trophoblastic glycoprotein 5T4, human