Pyloric metaplasia, pseudopyloric metaplasia, ulcer‐associated cell lineage and spasmolytic polypeptide‐expressing metaplasia: reparative lineages in the gastrointestinal mucosa

Abstract

Summary The gastrointestinal mucosae provide a critical barrier between the external and internal milieu. Thus, damage to the mucosa requires an immediate response to provide appropriate wound closure and healing. Metaplastic lineages with phenotypes similar to the mucous glands of the distal stomach or Brunner’s glands have been associated with various injurious scenarios in the stomach, small bowel and colon. These lineages have been assigned various names including pyloric metaplasia, pseudopyloric metaplasia, Ulcer-associated cell lineage (UACL) and spasmolytic polypeptide-expressing metaplasia (SPEM). A re-examination of the literature on these various forms of mucous cell metaplasia suggests that pyloric type mucosal gland lineages may provide a ubiquitous response to mucosal injury throughout the gastrointestinal tract as well as in the pancreas, esophagus and other mucosal surfaces. While the cellular origin of these putative reparative lineages likely varies in different regions of the gut, their final phenotypes may converge on a pyloric type gland dedicated to mucous secretion. In addition to their healing properties in the setting of acute injury, these pyloric type lineages may also represent precursors to neoplastic transitions in the face of chronic inflammatory influences. Further investigations are needed to determine how discrete molecular profiles relate to the origin and function of pyloric-type metaplasias previously described by histological characteristics in multiple epithelial mucosal systems in the setting of acute and chronic damage.

Spasmolytic polypeptide‐expressing metaplasia associated with higher expressions of miR‐21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives

“…Moreover, in the SPEM persist subjects, the posteradication chronic inflammatory scores remained higher in the both GCF and NUD control groups. Thus, these data supposed while SPEM in the stomach is initially reparative, their maintenance in the setting of chronic inflammation can contribute to further deleterious neoplastic scenarios …”

“…IM is a well‐established precursor for intestinal‐type gastric cancer. SPEM has gained attention as a neoplastic precursor, and chronic injury and inflammation may further promote SPEM development into IM and neoplasia . To the best of our knowledge, this is the first population‐based cohort study concerning familial clustering of gastric pyloric metaplasia and its association with H pylori infection.…”

“…[7][8][9][10] Spasmolytic polypeptide-expressing metaplasia (SPEM) was originally designated as pyloric metaplasia, pseudopyloric metaplasia, or antralization of corpus tissue as an initial metaplastic response to gastric injury, while chronic injury and inflammation may lead to the further development of IM from SPEM. 11 SPEM may be another preneoplastic metaplasia and is considered a potential early event in the cascade leading to the development of gastric cancer. 12,13 Because of higher occurrence of precancerous lesions in the relatives of patients with H pylori-related gastric cancer, the familial relatives of patients with gastric cancer are at high risk of gastric carcinogenesis.…”

Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium

“…The staining patterns for CD44v6, CD44v9, and CD44s on basolateral membranes were quite similar and nearly completely overlapped with GSII, while CD44v9 tended to produce a nonspecific signal in surface mucus (supplementary material, Figure S2E). Since TFF2, GSII, and CD44v9 are known to be expressed in SPEM and another SPEM marker, clusterin , was also broadly positive in the abnormal glands of Tff1‐Kras mice, the pseudopyloric glands in Tff1‐Kras mice contain SPEM at the gland base (supplementary material, Figure S2F). A subset of GSII‐positive cells was proliferating at the bottom of the corpus glands of Tff1‐Kras mice (Figure L).…”

“…In several mouse models with active Kras in the gastric epithelium, SPEM develops rapidly . SPEM represents a molecular representation of the histological description of pseudopyloric metaplasia, aberrant presence of antral‐type glands in the corpus . Several previous studies have been used to support the notion that chief or isthmus stem cells are the origin of metaplastic lesions .…”