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Gastric intestinal metaplasia: progress and remaining challenges

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Abstract

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.

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Acknowledgements

The authors thank the following support: ZNW by National Key Research and Development Program of China (No. 2022YFA1105300), National Natural Science Foundation of China (No.81961128026, No. U1908207), Overseas training project of Liaoning general higher education (No.2019GJWYB022); JCM by NIH National Cancer Institute R01CA246208; ZFM by National Natural Science Foundation of China (No.82072724), Department of Education of Liaoning Province (QNZR2020004, 2021-YQ-07); SJX by National Natural Science Foundation of China (No.82102686), and Joint Fund for the Cross-Disciplinary in Medicine and Engineering of Science and Technology Program Projects of Liaoning Province (No. 2021-YGJC-04).

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  1. Qi-Yue Tong, Min-Jiao Pang, and Xiao-Hai Hu have contributed equally to this article.

Authors and Affiliations

  1. Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China

    Qi-Yue Tong, Min-Jiao Pang, Xiao-Hai Hu, Xuan-Zhang Huang, Jing-Xu Sun, Xin-Yu Wang, Zhen-Ning Wang & Zhi-Feng Miao

  2. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China

    Qi-Yue Tong, Min-Jiao Pang, Xiao-Hai Hu, Xuan-Zhang Huang, Jing-Xu Sun, Xin-Yu Wang, Zhen-Ning Wang & Zhi-Feng Miao

  3. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA

    Joseph Burclaff

  4. Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA

    Joseph Burclaff

  5. Section of Gastroenterology and Hepatology, Department of Medicine, Departments of Pathology and Immunology, Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA

    Jason C. Mills

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Tong, QY., Pang, MJ., Hu, XH. et al. Gastric intestinal metaplasia: progress and remaining challenges. J Gastroenterol 59, 285–301 (2024). https://doi.org/10.1007/s00535-023-02073-9

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