Human monoclonal antibodies from stomach carcinoma patients react with Helicobacter pylori and stimulate stomach cancer cells in vitro.
BACKGROUND
In recent studies, an increased incidence of gastric adenocarcinomas was observed in patients with Helicobacter pylori infection. However, the extent to which this coincidence is caused by immunologic mechanisms is unknown.


METHODS
Two human monoclonal antibodies (MoAbs) from patients with stomach carcinoma and H. pylori-associated gastritis were isolated and established by fusion of spleen cells with the heteromyeloma HAB-1. The reactivity of these human MoAbs was investigated in functional adhesion assays and on Western blots of tissue, tumor cell, and bacterial extracts. Their stimulation and proliferation were tested by the MTT test and 3-H-thymidine incorporation tests.


RESULTS
The two monoclonal immunoglobulin-M antibodies, 103/51 and 105/79, inhibited adhesion of tumor cells. On bacterial extracts antibody 103/51 identified protein bands of 55 kilodaltons (kd) and 80 kd, and in tumor cell extracts, a specific protein of approximately about 110 kd and 140 kd. Antibody 105/79 identified a 55 kd protein in bacterial extracts and a 110 kd protein in tumor extracts. In addition, in the 3-H-thymidine incorporation and MTT assay the antibodies showed a stimulatory and growth-enhancing effect on tumor cells in vitro. A similar activity was observed in sera from patients with gastric carcinoma, indicating a physiologic role of such antibodies in vivo.


CONCLUSIONS
The human monoclonal antibodies described here react with H. pylori and cross-react with and stimulate gastric carcinoma cells. It is possible that the production of these antibodies is primarily stimulated by bacterial antigens which cause chronic gastritis and that they might be indirectly responsible for the recently described higher incidence of gastric cancer because of the simultaneous reaction and stimulation of tumor cells they cause.
Vollmers
H P
HP
Institut für Pathologie, Universität Würzburg, Germany.
Dämmrich
J
J
Ribbert
H
H
Grassel
S
S
Debus
S
S
Heesemannn
J
J
Müller-Hermelink
H K
HK
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002448:Cell Adhesion; D002455:Cell Division; D003429:Cross Reactions; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014316:Tritium; D006899:Mixed Function Oxygenases; D013936:Thymidine