A novel proliferation-associated variant of CFR-1 defined by a human monoclonal antibody

The germline coded human monoclonal IgM antibody 103/51 was isolated from a gastric carcinoma patient. This antibody binds to a 130-kd membrane molecu le and has a mitotic effect on tumor cells in vitro. To characterize the ta rget, we sequenced the protein and showed that the antibody binds to the cy steine-rich fibroblast growth factor receptor (CFR)-1, which is highly homo logous to MG-160 and the E-selectin-ligand (ESL)-1. The epitope was determi ned by glycosidase-digestion experiments to be an N-linked carbohydrate sid e chain. Immunohistochemistry was used to investigate the tissue distributi on of CFR-1. Different healthy tissues were tested and only the collecting tubes of the kidney, the Golgi apparatus, and the glomerular and fascicular zones of the adrenal gland stained positive. However, on malignant tissue the receptor is overexpressed in nearly all tested stomach cancers (12 of 1 5) and other tested carcinomas (13 of 15). Most interestingly, the receptor is also present in Helicobacter pylori gastritis and gastric dysplasia, bu t absent on uninflamed stomach mucosa. This restricted tissue pattern indic ates that antibody 103/51 reacts with a membrane-bound variant of CFR-1, wh ich is mainly expressed on transformed cells and precursor lesions and is e ssential for proliferation processes. The possible activity of antibody 103 /51 as an activating ligand in these proliferative changes of gastric epith elial mucosa is discussed.