Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

Simple Summary Generally, we know that cancers represent genetic changes in tumour cells, but we most often do not know the causes of cancers or how they develop. Our knowledge of the regulation of gastric acid secretion is well known, with the gastric hormone gastrin maintaining gastric acidity by stimulation of the enterochromaffin-like (ECL) cell to release histamine, which subsequently augments acid secretion. Furthermore, it seems to be a general principle that stimulation of function (which, for the ECL cell, is release of histamine) in a parallel way stimulates the proliferation of the same cell. Long-term hyperstimulation of cell division predisposes to genetic changes and, thus, development of tumours. All conditions with reduced gastric acidity result in an increased risk of gastric tumours due to elevated gastrin in order to restore gastric acidity. It is probable that Helicobacter pylori infection (the most important cause of gastric cancer), as well as drugs inhibiting gastric acid secretion induce gastric cancer in the long-term, due to an elevation of gastrin caused by reduced gastric acidity. Gastric carcinomas have been shown to express ECL cell markers, further strengthening this relationship. The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.