AUTOCRINE LOOP THROUGH CHOLECYSTOKININ-B GASTRIN RECEPTORS INVOLVED IN GROWTH OF HUMAN LEUKEMIA-CELLS/

The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormo nes, CCK and gastrin, with high affinities. These peptides have a trop hic effect on gastrointestinal cells expressing the receptor in vivo a s well as in vitro. Recently, this receptor mRNA was reported to be ex pressed in immunocytes localized in the lamina propria of normal rat s tomach mucose. Here, we studied the receptor expression in human hemat opoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorp honuclear (PMN) cells but not in the mononuclear cells of normal perip heral white blood cells by reverse transcription-polymerase chain reac tion. The receptor transcript was, however, expressed in human leukemi a cell lines (14 of 18 cell lines tested) derived from not only myeloi d, but also T- and B- lymphoid lineages. The CCK-B/gastrin receptors o n several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived me dium. Interestingly, a human CCK-B/gastrin receptor specific antagonis t, YM022, but not its stereotype isoform, selectively inhibited the DN A synthesis of THP-1, MOLT-II, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors. (C) 199 6 by The American Society of Hematology.