Role of mp 17O Seprase in Breast Cancer.

Seprase, a cell surface serine type gelatinase with MT 170 kDa whose expression is associated with melanoma invasiveness, is composed of two identical subunits of MT 97 kDa. Recent evidence indicated that the Seprase subunit is identical to Fibroblast Activation Protein a FAPa. To characterize and define the role of this molecule in cancer, human SepraseFAPa cDNA was cloned and stable transfected in two human epithelial carcinoma cell lines SW-13 and MCF-7. Unexpectedly, overexpression of SepraseFAPa has no apparent effect on the proliferation, matrix adhesion and matrigel invasion of these cells. Preliminary site-directed mutagenesis studies suggested that the region coding for the signalanchorage domain of the molecule and this intact domain are probably essential for SepraseFAPa mRNA stability and the dimerization of the subunits, respectively. Ribozyrne constructs targeted SepraseFAPa mRNAA have been made. However, despite the in vitro cleavage activity, these ribozyrne constructs are not effective in abrogating the endogenous SepraseFAPa level in highly metastatic melanoma l2O5LU cells.