Monocyte-related functions expressed in cell lines established from human pancreatic adenocarcinoma. II. Inhibition of stimulated activity by monoclonal antibodies reacting with surface antigens on tumor cells.

A previous study demonstrated that pancreatic tumor cells in culture but not other tumor cell lines, exhibit three major monocyte-related functions, i.e., endocytosis, lysosomal enzyme secretion, and luminol-enhanced chemiluminescence. All three functions could be stimulated to the same extent in pancreatic tumor cells as in monocytes by exposure to zymosan or immune complexes. In the present study, the effect of monoclonal antibodies (mabs) (BW 227/18 and BW 227/19), which react with epitopes on both monocytes and pancreatic tumor cells on basal and stimulated functions, was tested. Kinetic measurement of chemiluminescence showed a quick inhibition of this activity on both cell types within 3-5 min that amounted to approximately 50% of the basal activity and 60-90% of the stimulated activity. The same was true for inhibition of endocytotic activity and lysosomal enzyme secretion, which were inhibited to the same extent under both basal and stimulated conditions in monocytes as well as in pancreatic tumor cells. The biochemical measurements were supported by tracer studies using cationized ferritin and electronmicroscopy, demonstrating an inhibition of the uptake of tracer into multivesicular bodies by the addition of the two mabs. The inhibitory effect of the antibodies could reflect their binding to epitopes on the plasma membrane and an interference with membrane fluidity through cross-linking.