September 26, 2013

Cell changes en route to stomach cancer

Molecular characterization of pre-cancerous changes in cells lining the stomach could point to lesions with a greater risk of progression to cancer.

SPEM (spasmolytic polypeptide-expressing metaplasia) and intestinal metaplasia – pre-cancerous changes in the cells lining the stomach – are both associated with gastric cancer.

To more fully characterize different types of SPEM, James Goldenring, M.D., Ph.D., Paul W. Sanger Professor of Experimental Surgery, and colleagues compared the expression profiles of SPEM in three mouse models of acid-secreting parietal cell loss. They studied SPEM resulting from chronic infection with Helicobacter felis (similar to Helicobacter pylori) and from treatment-induced acute cell loss with or without inflammation.

They report in the September issue of the journal Gut that different types of SPEM have commonalities and differences in expression profiles. They found that the protein clusterin is a marker for all types of SPEM and also for poor prognosis of human gastric cancer. They showed that in mice, SPEM emerges after parietal cell loss and progresses to SPEM with characteristics of intestinal metaplasia when inflammation is present.

The findings suggest that detailed molecular characterization of SPEM could point to lesions with a greater risk of progression to dysplasia and cancer.

These studies were supported by grants from a Department of Veterans Affairs merit review award and by grants from the National Institutes of Health (DK071590, AI037750, ES002109, DK077065, CA095060).