CHOLECYSTOKININ B-TYPE RECEPTOR SIGNALING IS INVOLVED IN HUMAN PANCREATIC-CANCER CELL-GROWTH

Cholecystokinin (CCK) is known to stimulate pancreatic cancer cell gro wth, but no detailed CCK receptor subtype characterization and investi gation of CCK receptor-mediated cellular responses in human pancreatic cancer cells have been reported thus far. In this study, CCK binding sites were identified in human pancreatic cancer cells (MIA-PaCa-2) us ing radioligand binding studies. Pharmacological characterization demo nstrated a single class of high-affinity CCK sites on MIA-PaCa-2 cells (326 +/- 18 pM, receptor density 16.9 +/- 2.3 fmol/mg protein). These CCK binding sites displayed a typical CCKB binding profile as shown i n competition studies by using different CCK-related compounds and non -peptide CCK antagonists discriminating between CCKA and CCKB sites. C CKB receptor-connected effector systems have been characterized in MIA -PaCA-2 cells, and their involvement in CCK-8S-induced proliferative e ffects on MIA-PaCa-2 cells has been demonstrated.