Gastrins, cholecystokinins and gastrointestinal cancer

The gastrointestinal peptide hormones gastrin and cholecystokinin (CCK) are well known for their ability to stimulate gastric acid secretion and pancreatic enzyme secretion, respectively. The suggestion that gastrin and CCK might also promote the development of cancers of the gastrointestinal tract has been controversial, but an increasing body of evidence now supports the view that the amidated and nonamidated forms of gastrin act as growth factors via different receptors in different regions of the gut. For example, animal experiments indicate that amidated gastrins are involved in cellular differentiation and repair in the gastric mucosa, and synergise with Helicobacter pylori infection in the development of gastric carcinoma. In contrast, non-amidated gastrins stimulate colonic mucosal growth, accelerate the early steps in colorectal carcinoma formation, and are elevated in the tumour and circulation of patients with colorectal cancer. Although human pancreatic carcinomas express CCK-1 and CCK-2 receptors, the role of gastrins and CCK in pancreatic carcinogenesis is yet to be established. Further investigation of the possible role of the CCK-2 receptor in gastric and pancreatic neoplasia, and of the hypothesis that gastrin precursors act as autocrine growth factors in colorectal carcinoma, is warranted. However, therapies aimed at the gastrins must be targeted to the relevant gastrin/gastrin receptor combination. (C) 2004 Elsevier B.V. All rights reserved.