Human 5T4 oncofoetal
antigen defined by the murine 5T4
monoclonal antibody is a highly
glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some
cancers is associated with poor clinical outcome; overexpression of human 5T4
cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in
cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific
antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat
monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and
epitope mapped. Similar to its human counterpart, murine 5T4
antigen is a 72 kDa
glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10
melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4
antigen. The murine 5T4
antigen-expressing cell lines and antibody
reagents are now being used to explore novel
immunotherapies in pre-clinical models and the biology of 5T4 in development.