DEVELOPMENTALLY-REGULATED EXPRESSION OF METASTASIS-ASSOCIATED ANTIGENS IN THE RAT

The specificity of monoclonal antibodies (mABs) obtained after immuniz ation with a metastasizing rat tumor line was evaluated by screening e xpression in a variety of nonmetastasizing and metastasizing rat tumor lines. mABs, which by immunohistology and Western blotting recognized metastasizing lines, were used to define the physiological expression of the corresponding antigens during ontogeny as well as in adult rat s. From a panel of 12 mABs, 2 recognized structures on metastasizing a nd nonmetastasizing tumor lines, while 10 stained exclusively metastas izing lines. Five of the latter bound to tumor lines metastasizing eit her hematogenously or via the lymphatic system. All five recognized an epitope on CD44 variant exon v6. The five remaining mABs, recognizing four independent antigenic entities, only stained tumor lines metasta sizing via the lymphatics. Surprisingly, these antigens were also dete cted in normal tissues: three on epithelial cells either widespread or of the upper gastrointestinal tract or the urogenital system, the fou rth preferentially on epithelial cells, but also on nerves and hematop oietic precursor cells, and the fifth on many tissues and cells with a predominance of mesenchyme-derived structures. Notably, during ontoge ny, expression of these five antigens was induced in different compart ments of the developing fetal and/or maternal part of the placenta. Th e five newly described metastasis-associated antigens share with CD44v the absence of expression on nonmetastasizing tumor lines as well as expression on distinct, nontransformed cells and induction of expressi on during ontogeny. Thus, tumor progression may rather be initiated by inappropriate expression or up-regulation of genes, which do not disp lay transforming features, than by de novo appearance of ''metastasis genes.'' Accordingly, metastasizing tumor lines may be a valuable tool to identify developmentally regulated gene products.