The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive in vitro and in vivo studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.
Keywords: CCK; G protein-coupled receptor; cancer; gastrin; imaging; therapeutics.
Copyright © 2020 Zeng, Ou, Wang and Guo.
Gastrin, CCK, signaling, and cancer.Annu Rev Physiol. 2001;63:49-76. doi: 10.1146/annurev.physiol.63.1.49. Annu Rev Physiol. 2001. PMID: 11181948 Review.
Cholecystokinin-B (CCK-B)/gastrin receptor targeting peptides for staging and therapy of medullary thyroid cancer and other CCK-B receptor expressing malignancies.Biopolymers. 2002;66(6):399-418. doi: 10.1002/bip.10356. Biopolymers. 2002. PMID: 12658727
Differential expression of gastrin, cholecystokinin-A and cholecystokinin-B receptor mRNA in human pancreatic cancer cell lines.Scand J Gastroenterol. 2001 Jul;36(7):738-43. doi: 10.1080/003655201300192003. Scand J Gastroenterol. 2001. PMID: 11444473
The role of gastrin and cholecystokinin in normal and neoplastic gastrointestinal growth.J Gastroenterol Hepatol. 1995 Mar-Apr;10(2):215-32. doi: 10.1111/j.1440-1746.1995.tb01083.x. J Gastroenterol Hepatol. 1995. PMID: 7787172 Review.
Cellular localization of cholecystokinin receptors as the molecular basis of the periperal regulation of acid secretion.Pharmacol Toxicol. 2002 Dec;91(6):351-8. doi: 10.1034/j.1600-0773.2002.910612.x. Pharmacol Toxicol. 2002. PMID: 12688378 Review.