Similarities in function between pancreatic tumor cells and macrophages and their inhibition by murine monoclonal antibodies.
Fine structural studies of human pancreatic adenocarcinomas have demonstrated their composition of one major secretory cell type, a mucin secreting cell. It was also demonstrated that pancreatic tumor cells have a high endocytotic activity via the regular endocytotic pathway with uptake via coated pits and vesicles. These findings indicate a striking similarity between pancreatic tumor cells and human mononuclear phagocytes. Therefore monocyte-related functions like endocytosis, lysosomal enzyme secretion and superoxide anion production were measured in various cell lines of human pancreatic adenocarcinomas in comparison to human mononuclear phagocytes. These functions were measured under basal conditions and after exposure to zymosan or immune complexes. All pancreatic tumor cells tested demonstrated increased endocytotic, secretory and oxidative burst activity to a similar extent as human mononuclear phagocytes after exposure to the stimuli (zymosan or immune complexes). In a further attempt murine monoclonal antibodies produced against pancreatic tumor cells were characterized in relation to their tissue specificity, the epitope recognized in in vitro and in vivo radiolocalization and their potential to mediate biological functions (e.g. antibody dependent cellular cytotoxicity or complement mediated cytolysis). Mouse monoclonal IgG1 antibodies which specifically bind to the majority of well differentiated adenocarcinomas of the human pancreas as well as to human mononuclear phagocytes have been shown to inhibit several cellular functions (lysosomal enzyme release, pinocytosis of colloidal gold 198Au, and chemiluminescence) of those cells. Incubation of 10 micrograms/ml of monoclonal IgG1 antibody with pancreatic tumor cell lines or human monocytes either simultaneous or followed by the stimulation with zymosan (50 micrograms/ml) or immune complexes (100 micrograms/ml) resulted in the inhibition of lysosomal enzyme release and uptake of colloidal radioactive gold of both human mononuclear phagocytes and pancreatic tumor cells responding to zymosan or immune complexes. In addition those monoclonal antibodies have been found to inhibit luminol-dependent chemiluminescence. Kinetic measurements of chemiluminescence showed a quick inhibition of this activity on both cell types within 1 to 3 minutes. Antibody F(ab')2 fragments behaved analogously to the whole antibodies, whereas monovalent Fab fragments were not able to inhibit any of the mentioned functions. When used alone the monoclonal antibodies were not cytotoxic and did not theirselves trigger release of acid hydrolases, did not alter pinocytosis and did not induce oxidative metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
Schorlemmer
H U
HU
Research Laboratories of Behringwerke AG, Marburg, W. Germany.
Bosslet
K
K
Kern
H F
HF
Sedlacek
H H
HH
D000230:Adenocarcinoma / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D006801:Humans; D008163:Luminescent Measurements; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*; D010587:Phagocytosis
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; C042317:DU-PAN-2 antigen, human