Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Screening for surface molecules expressed by metastasizing rat tumors had r evealed evidence for metastasis-association of a molecule also expressed on epithelial cells. The similarity to the expression profile of the panepith elial glycoprotein EGP314 prompted us to isolate and sequence the gene and to explore functional features of the molecule in transfected tumor lines. The molecule D5.7A, named according to the antibody, D5.7, used for selecti on, indeed, is the ortholog of EGP314 with 92% and 80% identity to the muri ne and the human molecules. Like EGP314, D5.7A has a particular cleavage si te, a small cleavage product being resolved under reducing conditions from the membrane anchored part of the molecule. Transfection of a low metastasi zing fibrosarcoma, pheochromoblastoma and adenocarcinoma revealed that expr ession of D5.7A facilitates tumor progression. Depending on the origin of t he tumor, D5.7A transfectants either metastasized via the lymphatic system (pheochromoblastoma, adenocarcinoma) or hematogeneously (fibrosarcoma). Par ticularly after proteolytic cleavage, D5.7A facilitated cell - cell adhesio n and provided a proliferative signal upon crosslinking. Thus, the rat orth olog of EGP314 is involved in metastasis formation. Importantly, its functi onal activities apparently rely on proteolytic cleavage. These findings pro vide a first evidence on how a panepithelial marker can be involved in tumo r progression.