Gastric carcinogenesis involves the loss of parietal cells (oxyntic atrophy) and subsequent replacement of the normal gastric lineages with metaplastic cells. In humans, two metaplastic lineages develop as sequelae of chronic Helicobacter pylori infection: intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia (SPEM). Mouse models of both chronic Helicobacter infection and acute pharmacological oxyntic atrophy have led to the discovery that SPEM arises from transdifferentiation of mature chief cells. The presence of inflammation promotes the expansion of SPEM in mice. Furthermore, studies in Mongolian gerbils as well as increasing evidence from human studies indicate that SPEM likely represents a precursor for the development of intestinal metaplasia. These findings suggest that loss of parietal cells, augmented by chronic inflammation, leads to a cascade of metaplastic events. Identification of specific biomarkers for SPEM and intestinal metaplasia hold promise for providing both early detection of preneoplasia and information on prognostic outcome following curative resection.
|Title of host publication||Progress in Molecular Biology and Translational Science|
|Number of pages||15|
|Publication status||Published - 2010|
|Name||Progress in Molecular Biology and Translational Science|
Bibliographical noteFunding Information:
Dr. Goldenring is supported by grants from a Department of Veterans Affairs Merit Review Award, RO1 DK071590 from the National Institutes of Health, the AGA Funderburg Award in Gastric Biology Related to Cancer, and core resources of the Vanderbilt Digestive Disease Center, P30 DK058404.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology