Cholecystokinin analog, JMV-180, stimulates growth of human pancreatic cancer.
The gastrointestinal peptide CCK has been shown to stimulate growth of normal and malignant pancreatic tissue. The CCK receptor possesses several different binding sites for CCK. By using the CCK analog JMV-180, which is a functional agonist at CCK high- and low-affinity receptors and an antagonist at very low affinity receptors, and carbachol, which down-regulates binding to CCK high-affinity receptors, we evaluated which receptor is involved in growth of human pancreatic cancer cells. PANC-1 and MIA PaCa-2 human pancreatic cancer cell lines were grown for four to six days in the presence or absence of JMV-180 (10(-10)-10(-6) M) alone or in combination with carbachol (10 mM). Growth was evaluated by counting cells and by [3H]thymidine incorporation. JMV-180 increased cell number in PANC-1 and MIA PaCa-2 cells 123% and 86%, respectively, over controls (P = 0.004). DNA synthesis by [3H]thymidine uptake was increased 64% and 40% in PANC-1 and MIA PaCa-2 cells, respectively, over controls (P < 0.001). The trophic effect of JMV-180 was not inhibited by the addition of carbachol. Since JMV-180 stimulated the growth and since the effect was not inhibited by carbachol, we suggest that the growth effects of CCK in pancreatic cancer cells are mediated by the low-affinity receptor.
Swift
I R
IR
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Smith
J P
JP
D002217:Carbachol / Q000494:pharmacology; D002452:Cell Count; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011949:Receptors, Cholecystokinin / Q000502:physiology; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011949:Receptors, Cholecystokinin; C058451:JMV 180; D002217:Carbachol; D012844:Sincalide