[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332248-105":59,"doc-detail-332248-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","regulation-of-metaplasia-and-dysplasia-in-the-stomach-by-the-stromal-microenvironment","Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment","","Research on the microenvironment linked to gastric carcinogenesis has often focused on established stomach cancers while underestimating premalignant stages such as metaplasia and dysplasia. Because epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells are crucial for precancerous lesion formation, clarifying cellular crosstalk is needed. This review highlights how stromal fibroblast subpopulations shape epithelial transformation during precancerous stages, outlines possible tumor-promoting fibroblast targets, and identifies open questions on fibroblast plasticity and modulation of gastric carcinogenesis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/regulation-of-metaplasia-and-dysplasia-in-the-stomach-by-the-stromal-microenvironment/332248/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/regulation-of-metaplasia-and-dysplasia-in-the-stomach-by-the-stromal-microenvironment/332248.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the stromal microenvironment important in gastric precancerous progression?","Question",{"text":112,"@type":113},"Epithelial interactions with immune cells are essential for forming precancerous lesions, yet the specific influence of stromal cells such as fibroblasts on epithelial transformation during premalignant stages remains unclear.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What characterizes pyloric metaplasia?",{"text":117,"@type":113},"Pyloric metaplasia arises after loss of acid-secreting parietal cells, involving reprogramming of digestive enzyme-secreting cells into mucus-secreting cells and formation of SPEM lineages at the gland base plus foveolar hyperplasia at the gland top.",{"name":119,"@type":110,"acceptedAnswer":120},"How do complete and incomplete intestinal metaplasia differ in risk and prognosis?",{"text":121,"@type":113},"Incomplete intestinal metaplasia shows a hybrid mixture of gastric and intestinal-like lineages and carries the greatest risk of progression to dysplasia or gastric cancer, whereas complete intestinal metaplasia has lower risk and better prognosis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332248,1790139491,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","[www.nature.com/emm](www.nature.com/emm)  \nREVIEW ARTICLE OPEN   \nRegulation of metaplasia and dysplasia in the stomach by the stromal microenvironment  \nJared D. Rhodes1,2, James R. Goldenring1,2,3,4,5 ✉ and Su-Hyung Lee 2,3 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| the modulation of gastric carcinogenesis. |  |  |\n|  | Experimental & Molecular Medicine (2024) 56:1322–1330; [https://doi.org/10.1038/s12276-024-01240-z](https://doi.org/10.1038/s12276-024-01240-z) |  |\n|  |  |  |\n\nINTRODUCTION  \nProgression of metaplasia to dysplasia  \nMetaplasia is a response to injury and a process by which normal mature cells of one tissue lineage are replaced by cells resembling a dissimilar and differentiated cell type observed in other tissues1. The metaplastic response represents the most extensive example of lineage adaptation to acute and chronic injury in the stomach. Importantly, the stomach is frequently exposed to harsh insults, and metaplasia serves to protect damaged tissue in part via mucin production. In response to damage to the stomach, two different types of metaplastic lineages repopulate the gastric mucosa: pyloric metaplasia and intestinal metaplasia2.  \nPyloric metaplasia represents the initial response to the loss of acid-secreting parietal cells through the reprogramming of digestive enzyme-secreting cells into mucus-secreting cells atthe base of the gastric corpus glands (Fig. 1)2. The reprogramming of lineages at the base of pyloric metaplasia glands is characteristic of spasmolytic polypeptide-expressing metaplasia (SPEM), which was first identified in 1999 following investigationsin which mice and humans infected with Helicobacter felis (H. felis) or H. pylori, respectively, that showed atypical expression of amucinous spasmolytic polypeptide (trefoil factor 2; TFF2) at the base of damaged glands3,4. Common markers of SPEM cell lineages in humans and mice include CD44v9, aquaporin 5 (AQP5), and gastric intrinsic factor (GIF)/Griffonia simplicifolia lectin II (GSII) co-positivity5. Additionally, pyloric metaplasia exhibits an expansion of foveolar cells at the top of the gland, which is termed  \nfoveolar hyperplasia. Thus, pyloric metaplasia contains both foveolar hyperplasia toward the top of the gland and SPEM cell lineages at the bottom (Fig. 1) .  \nIntestinal metaplasia subsequently develops in the context of chronic and unresolved injury, whereby cells with intestinal characteristics populate the gastric glands. Notably, intestinal metaplasia is commonly characterized by the appearance of MUC2-expressing goblet cells (Fig. 1)2. There are tw","cbCaigojkIv2naND","https://ap.wps.com/l/cbCaigojkIv2naND","pdf",1821793,"English","# Introduction\n## Progression of metaplasia to dysplasia\n### Pyloric metaplasia\n### Intestinal metaplasia\n### Dysplasia","[{\"question\":\"Why is the stromal microenvironment important in gastric precancerous progression?\",\"answer\":\"Epithelial interactions with immune cells are essential for forming precancerous lesions, yet the specific influence of stromal cells such as fibroblasts on epithelial transformation during premalignant stages remains unclear.\"},{\"question\":\"What characterizes pyloric metaplasia?\",\"answer\":\"Pyloric metaplasia arises after loss of acid-secreting parietal cells, involving reprogramming of digestive enzyme-secreting cells into mucus-secreting cells and formation of SPEM lineages at the gland base plus foveolar hyperplasia at the gland top.\"},{\"question\":\"How do complete and incomplete intestinal metaplasia differ in risk and prognosis?\",\"answer\":\"Incomplete intestinal metaplasia shows a hybrid mixture of gastric and intestinal-like lineages and carries the greatest risk of progression to dysplasia or gastric cancer, whereas complete intestinal metaplasia has lower risk and better prognosis.\"}]","Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment | PDF",1789997520,23]