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.