REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642559
This article is part of the Research TopicChronic Atrophic Gastritis: Pathogenesis, Diagnostic Challenges, and Gastric Cancer RiskView all 9 articles
Cellular Lineage Origins of Spasmolytic Polypeptide-Expressing Metaplasia (SPEM): Persistent and Intensifying Debates
Provisionally accepted
- 1Heilongjiang University of Chinese Medicine, Harbin, China
- 2First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, China
- 3Guangzhou University of Traditional Chinese Medicine Shenzhen Hospital, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) is a gastric fundic gland metaplasia resembling deep antral glands, associated with drug injury, Helicobacter pylori (H. pylori), or bile reflux. Early-stage SPEM acts as a reparative response, but if the damaging stimuli persist, the metaplastic changes may become irreversible, raising the risk of gastric cancer development. Traditionally, SPEM arises via passive transdifferentiation of chief cells following parietal cell loss. However, recent lineage tracing and genetic models challenge this, suggesting active depletion of chief cells and involvement of isthmus stem cells also contribute to SPEM development, intensifying debate over its cellular origins. This review synthesizes SPEMs physicochemical drivers and critically evaluates evidence for the three proposed sources: (1) passive chief cell transdifferentiation, (2) active chief cell loss, and (3) isthmus stem cells. Clarifying the heterogeneity in the origin of SPEM is challenging until more specific cell ablation techniques are developed, but timely classification of existing research may be instructive.
Keywords: Spasmolytic polypeptide-expressing metaplasia (SPEM), gastric cancer, Metaplasia, Cellular Lineage, Precancerous lesion
Received: 06 Jun 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Li, Li, Wu, Wang, Huang, Rong, Shen, Ma and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Zhang, yangzhang83@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.