VIP regulation of a human pancreatic cancer cell line: Capan-1.
VIP and secretin control the secretory function of the normal pancreas. We analysed their regulatory functions in a human pancreatic cancer cell line: Capan-1. Saturation binding experiments with 125I-VIP showed the existence of one class of binding sites of very high affinity: KD 6.4 +/- 3.0 X 10(-11) M and a low Bmax: 12 fmoles/10(6) cells, in both intact cells and membrane preparations. This site has not yet been described in normal or tumorous digestive cells. Competition binding experiments let us characterize two more binding sites, KD: 2.1 +/- 0.7 X 10(-9) M and 5.0 +/- 0.6 X 10(-8) M and the corresponding Bmax: 120 and 500 fmoles/10(6) cells. These sites are similar to those found on cells of the digestive tract. Competition binding experiments gave the following IC50: 3.0 +/- 0.9 X 10(-9) M for VIP; 2 +/- 0.6 X 10(-6) M for PHI; and 1 +/- 0.7 X 10(-5) M for secretin. VIP elicited a cAMP rise, the half maximal response being obtained at 1.2 X 10(-10) M. Secretin induced a cAMP response but only for concentrations higher than 10(-8) M. VIP receptors were found to be modulated by two factors: cell ageing and cell density. Cells chronically treated with VIP showed a slight decrease of their proliferation; insulin exerted an opposite effect. It is concluded that at the difference of normal pancreatic cells, the present cell line lacks secretin-preferring receptors and acquires some of the properties of intestinal cells.
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010451:Peptide PHI; D010455:Peptides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin / Q000378:metabolism / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D010451:Peptide PHI; D010455:Peptides; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP