The promoter of somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers.
While epidemiological evidence from patients with elevated serum gastrin levels related to pernicious anaemia does not support an increased risk for colon cancer, a recent study suggests that prolonged hypergastrinaemia is associated with an increased risk for colon cancer.
Our findings show that physiological doses of incompletely processed form of gastrin induce the invasiveness of tumor cells in vitro and suggest a novel potential role for this peptide in the metastatic process of colonic cancers in vivo.
The growth of colon cancer was promoted by the application of gastrin, whereas it was restricted by proglumide, which is known to be a gastrin receptor antagonist.
Previous studies have shown that the gene encoding the hormone gastrin is activated during colon cancer progression and the less-processed forms of gastrin are important colonic trophic factors.
Thus low to moderate levels of gastrin were expressed by human colon cancer cell lines which may function as autocrine growth factors for colon cancers.
To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present.
The hyperplastic response of the fundic mucosa was increased by increasing gastrin doses; whereas, colon cancer hyperplasia was maximal at the lowest dose tested (125 micrograms/kg/day) and did not increase further with increasing doses of hormone.