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 cells and is currently used in a clinical Phase II trial. The antibody binds to a target molecule that is preferentially expressed on diffuse- and intestinal-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 receptor is a stomach carcinoma-associated isoform of CD55 [membrane-bound decay-accelerating factor (DAF)-B] with a relative molecular mass of approximately 82 kDa. The antigenic site of SC-1 is an N-linked carbohydrate residue. Cross-linking of the DAF receptor increases apoptotic activity. SC-1 binding induces tyrosine phosphorylation of three proteins of approximately 60, 75, and 110 kDa, whereas a serine residue of an approximately 35-kDa protein is dephosphorylated. Expression of caspase-3 (CPP32) and caspase-8 (FLICE) is elevated, and activation of these caspases occurs. These data show that a tumor-specific variant form DAF is involved in apoptosis and can be used for adjuvant therapeutical purposes on gastric carcinoma.
Hensel
F
F
Institut für Pathologie, Würzburg, Germany.
Hermann
R
R
Schubert
C
C
Abé
N
N
Schmidt
K
K
Franke
A
A
Shevchenko
A
A
Mann
M
M
Müller-Hermelink
H K
HK
Vollmers
H P
HP
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000912:Antibodies, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D017209:Apoptosis; D018958:CD55 Antigens / Q000302:isolation & purification / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000502:physiology*; D006801:Humans; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D018958:CD55 Antigens; D017261:Glycosylphosphatidylinositols; D010738:Type C Phospholipases; D006026:Glycoside Hydrolases; D020169:Caspases; D043265:Phosphatidylinositol Diacylglycerol-Lyase