AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 1 135-R141, Copyright © 1995 by American Physiological Society
Identification of gastrin as a growth peptide in human pancreatic cancer
J. P. Smith, A. P. Fantaskey, G. Liu and I. S. Zagon
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
The present study reports the first evidence that the gastrointestinal
peptide gastrin stimulates the growth of several human pancreatic cancer
cells in culture and in tumors transplanted to nude mice. Gastrin promoted
growth of all cell lines tested at a dose comparable to the binding
affinity, providing evidence for a physiologically relevant receptor. The
stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor
antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718.
Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting
that gastrin is tonically produced by PANC-1 cells for regulation of
growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24
days subcutaneously with either 1% bovine serum albumin (diluent),
pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the
pentagastrin-treated mice were found to weigh more and have greater protein
and DNA content than controls, whereas these values were all decreased in
tumors of L-365,260-treated mice. Receptor binding capacity changed in
tumors of animals treated with the peptide or antagonist, suggesting a
regulatory process. Gastrin immunoreactivity was detected in a transplanted
PANC-1 human tumor. These results identify gastrin as a potent trophic
peptide that actively stimulates growth of human pancreatic cancer and does
so through a CCK-B/gastrin-like receptor.
