Spasmolytic polypeptide expressing metaplasia to preneoplasia in H-felis-infected mice

Background & Aims: The emergence of oxyntic atrophy and metaplastic cell lineages in response to chronic Helicobacter pylori infection predisposes to gastric neoplasia. We have described a trefoil factor family 2 (TFF2; spasmolytic polypeptide) expressing metaplasia (SPEM) associated with gastric neoplasia in both rodent and human fundus. To examine the relationship of SPEM to the neoplastic process in the H. felis-infected C57BL/6 mouse, we have now studied the association of SPEW related transcripts with preneoplasia. Methods: SPEW related transcripts were identified by microarray analysis of amplified cRNA from SPEM, and surface mucous cells were isolated by laser capture microdissection from the same gastric sections from male C57BL/6 mice infected with H. felis for 6 months. Expression of SPEM-related transcripts was assessed by in situ hybridization and quantitative RT-PCR, as well as immunohistochemistry for prothymosin alpha. Results: Eleven SPEW related transcripts were identified as detectable only in SPEM. The expression of the SPEM-related transcripts was validated by in situ hybridization and quantitative PCR. One transcript, the noncoding RNA Xist, was only identified in SPEM cells from the infected male mice. Ten of the 11 transcripts as well as TFF2 were also expressed in regions of gastritis cystica profunda. lmmunocytochemistry for one of the identified proteins, prothymosin alpha, demonstrated prominent nuclear staining in SPEM and gastritis cystica profunda. Conclusions: The expression of SPEM-related transcripts in regions of gastritis cystica profunda suggests that SPEM represents a precursor lineage for the development of dysplasia in this animal model of gastric carcinogenesis.