Characterization of glycosylphosphatidylinositol-linked molecule CD55/decay-accelerating factor as the receptor for antibody SC-1-induced apoptosis

The human monoclonal antibody SC-1 induces apoptosis of stomach carcinoma c ells and is currently used in a clinical Phase II trial. The antibody binds to a target molecule that is preferentially expressed on diffuse- and inte stinal-type stomach cancer cells and shows a very restricted expression on other normal and malignant tissues. In this paper, we show that the SC-1 re ceptor is a stomach carcinoma-associated isoform of CD55 [membrane-bound de cay-accelerating factor (DAF)-B] with a relative molecular mass of approxim ately 82 kDa, The antigenic site of SC-1 is an N-linked carbohydrate residu e. Cross-linking of the DAP receptor increases apoptotic activity. SC-1 bin ding induces tyrosine phosphorylation of three proteins of approximately 60 , 75, and 110 kDa, whereas a serine residue of an approximately 35-kDa prot ein is dephosphorylated, Expression of caspase-3 (CPP32) and caspase-8 (FLI CE) is elevated, and activation of these caspases occurs. These data show t hat a tumor-specific variant form DAF is involved in apoptosis and can be u sed for adjuvant therapeutical purposes on gastric carcinoma.