Effect of gastrin-releasing peptide on the pancreatic tumor cell line (Capan).
Gastrin-releasing peptide (GRP) has previously been shown to be an autocrine growth factor for small cell lung cancer, and our objective in the study presented here was to determine whether GRP has a similar role in pancreatic cancer. Using 125I-GRP, we demonstrated binding to specific, saturable, high-affinity sites (Kd = 1 nM; Bmax = 245 fmol/mg protein) in membrane preparations from the pancreatic tumor cell line Capan. The receptors were found to be biologically active. In whole cells, a GRP analogue bound to these receptors and stimulated rapid transfer of tritium from the tritiated lipid inositol pool to inositol triphosphates. Exogenous GRP addition stimulated incorporation of [3H]thymidine into DNA 20-60%. This stimulatory effect was blocked by the addition of a monoclonal antibody that complexed specifically with the receptor-binding portion of the peptide. In addition, the monoclonal antibody inhibited the growth of Capan cells in an in vitro growth assay without exogenous peptide. Bombesin receptor-specific antagonists also inhibited growth in a similar fashion. These data suggest that paracrine production of GRP may be important in pancreatic tumor growth, or that low-levels of a GRP-like peptide may play an autocrine role in this tumor.
Avis
I
I
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850.
Jett
M
M
Kasprzyk
P G
PG
Cuttitta
F
F
Treston
A M
AM
Maneckjee
R
R
Mulshine
J L
JL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D001839:Bombesin / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D005755:Gastrins; D007457:Iodine Radioisotopes; D010455:Peptides; D007294:Inositol; D019886:Gastrin-Releasing Peptide; D001839:Bombesin