NEW INSIGHTS INTO THE STEM-CELLS AND THE PRECURSORS OF THE GASTRIC EPITHELIUM

It is believed that stomach neoplasia represents the end result of a m ultistep journey that starts with derangement of the cellular prolifer ation and commitment program of the epithelium. The epithelium is norm ally made up of a single layer of cells that invaginates to form numer ous short pits continuous with long tubular glands divisible into isth mus, neck, and base regions. Three main cell lineages populate these p it-gland units: 1) mucus-secreting pit, 2) pepsinogen-secreting zymoge nic, and 3) acid-secreting parietal cell lineages. The immature cells of,the unit are located in the isthmus region; they include undifferen tiated stem cells that undergo frequent asymmetric mitosis to reproduc e themselves and give rise to two partially committed precursors: 1) p repit-cell precursors, which become prepit cells in the isthmus and th en migrate outward into the pit and mature into pit cells, and 2) pren eck cell precursors, which become preneck cells in the isthmus and the n migrate inward to the neck region and transform into neck cells. The latter continue their inward migration and eventually reach the base region where they gradually change their phenotype through a prezymoge nic step to become zymogenic cells. The stem cells, as well as the pre pit and preneck cell precursors, share in the production of preparieta l cells that, in the isthmus, mature into parietal cells and then migr ate outward into the pit or inward into the neck and base. The stem ce lls also give rise to preenteroendocrine and precaveolated cells. Thes e become, respectively, enteroendocrine and caveolated cells that proc eed to follow the bidirectional migratory route of parietal cells. The production of rare nonproliferating preparietal cells is enhanced aft er blocking the secretory activity of their mature forms by continuous infusion of the histamine H-2-receptor antagonist, ranitidine, for 42 h. Thus, the presence of active mature parietal cells is necessary to maintain the normal cellular proliferation and commitment program in the gastric epithelium.