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Characterization of glycosylphosphatidylinositol-linked molecule CD55/decay-accelerating factor as the receptor for
F Hensel1, R Hermann, C Schubert
1Institut für Pathologie, Würzburg, Germany.
Abstract:
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.
Insights
The human monoclonal antibody SC-1 targets a unique stomach cancer cell receptor, a variant of CD55 (decay-accelerating factor). This antibody triggers cancer cell death, offering potential for gastric carcinoma treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Human monoclonal antibody SC-1 induces apoptosis in stomach carcinoma cells.
- SC-1 targets a molecule preferentially expressed on diffuse- and intestinal-type stomach cancers with restricted normal tissue expression.
Purpose of the Study:
- Identify the SC-1 receptor.
- Elucidate the mechanism of SC-1-induced apoptosis in gastric carcinoma.
Main Methods:
- Immunoprecipitation and Western blotting to identify the SC-1 receptor.
- Analysis of protein phosphorylation and caspase activation.
- Assessment of SC-1 binding and receptor cross-linking effects.
Main Results:
- The SC-1 receptor is identified as a stomach carcinoma-associated isoform of CD55 (DAF-B), approximately 82 kDa.
- SC-1's antigenic site is an N-linked carbohydrate residue.
- SC-1 binding induces tyrosine phosphorylation of specific proteins and dephosphorylation of another, alongside elevated expression and activation of caspases-3 and -8.
Conclusions:
- A tumor-specific variant of DAF is involved in gastric carcinoma apoptosis.
- SC-1 shows potential as an adjuvant therapeutic agent for gastric carcinoma.