A Novel Proliferation-Associated Variant of CFR-1 Defined by a Human Monoclonal Antibody

• Published in: Laboratory investigation 2001-08, Vol.81 (8), p.1097-1108
• Main Authors: Hensel, Frank, Brändlein, Stephanie, Eck, Matthias, Schmidt, Karsten, Krenn, Veit, Kloetzer, Astrid, Bachi, Angela, Mann, Matthias, Müller-Hermelink, Hans Konrad, Vollmers, H Peter
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Animals; Antibodies, Monoclonal - immunology; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antigens, Neoplasm - isolation & purification; Autoantibodies - immunology; Biological and medical sciences; Cell Line; Epitopes - immunology; Gastric Mucosa - chemistry; Gastroenterology. Liver. Pancreas. Abdomen; Glycoside Hydrolases - chemistry; Humans; Immunohistochemistry; Laboratory Medicine; Medical sciences; Medicine; Medicine & Public Health; Mice; Oligonucleotides, Antisense; Pathology; Receptors, Fibroblast Growth Factor - genetics; Receptors, Fibroblast Growth Factor - immunology; Receptors, Fibroblast Growth Factor - isolation & purification; Stomach Neoplasms - chemistry; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tissue Distribution; Transfection; Tumors
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3780322

The germline coded human monoclonal IgM antibody 103/51 was isolated from a gastric carcinoma patient. This antibody binds to a 130-kd membrane molecule and has a mitotic effect on tumor cells in vitro. To characterize the target, we sequenced the protein and showed that the antibody binds to the cysteine-rich fibroblast growth factor receptor (CFR)-1, which is highly homologous to MG-160 and the E-selectin-ligand (ESL)-1. The epitope was determined by glycosidase-digestion experiments to be an N-linked carbohydrate side chain. Immunohistochemistry was used to investigate the tissue distribution 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 15) and other tested carcinomas (13 of 15). Most interestingly, the receptor is also present in Helicobacter pylori gastritis and gastric dysplasia, but absent on uninflamed stomach mucosa. This restricted tissue pattern indicates that antibody 103/51 reacts with a membrane-bound variant of CFR-1, which is mainly expressed on transformed cells and precursor lesions and is essential for proliferation processes. The possible activity of antibody 103/51 as an activating ligand in these proliferative changes of gastric epithelial mucosa is discussed.