[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-372406-105":59,"doc-detail-372406-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","dipeptidase-1-knockout-mice-develop-invasive-tumors-with-features-of-microsatellite-unstable-colorectal-cancer","Dipeptidase-1–knockout mice develop invasive tumors with features of microsatellite-unstable colorectal cancer","","Dipeptidase-1 (DPEP1) is strongly upregulated in colorectal cancer (CRC) and has been linked to invasion and metastasis. Neutrophils can promote tumor growth, yet it is unclear whether they directly interact with DPEP1-expressing CRC cells and how this affects CRC characteristics. Here, neutrophils bind DPEP1-expressing CRC cells, and DPEP1 shows preference for microsatellite-stable tumors. Carcinogen-treated Dpep1-null mice develop distal colon invasive adenocarcinomas and squamous cancers with MSI-H-like immune changes.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dipeptidase-1-knockout-mice-develop-invasive-tumors-with-features-of-microsatellite-unstable-colorectal-cancer/372406/",{"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/dipeptidase-1-knockout-mice-develop-invasive-tumors-with-features-of-microsatellite-unstable-colorectal-cancer/372406.png","ImageObject",300,407,{"name":92,"@type":93},"Alex Sinclair","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main role proposed for Dipeptidase-1 (DPEP1) in colorectal cancer?","Question",{"text":112,"@type":113},"DPEP1 is highly upregulated in CRC and is linked to invasion and metastasis. The study further explores DPEP1 as a receptor involved in shaping interactions with neutrophils and the tumor microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Do neutrophils bind to DPEP1-expressing colorectal cancer cells?",{"text":117,"@type":113},"Yes. The study shows that neutrophils bind DPEP1-expressing CRC cells, supporting a direct connection between DPEP1 expression and neutrophil engagement.",{"name":119,"@type":110,"acceptedAnswer":120},"How does DPEP1 expression relate to microsatellite stability and immune infiltration?",{"text":121,"@type":113},"DPEP1 is preferentially expressed in microsatellite-stable (MSS) CRCs, which show fewer CD8+ T cells, and it is negatively correlated with microsatellite-unstable (MSI-H) CRCs, which are T cell rich and more responsive to immunotherapy.","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},372406,1790766780,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099523882182,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","RESE AR CH  \nARTICLE  \nConflict of interest: The authors have declared that no conflict of interest exists.  \nCopyright: © 2025, Glass et al. This isan open access article published under the terms of the Creative Commons Attribution 4.0 International License.  \nSubmitted: September 11, 2024  \nAccepted: March 27, 2025  \nPublished: April 3, 2025  \nReference information: JCI Insight. 2025;10(9):e186938 .  \n[https://doi.org/10.1172/jci](https://doi.org/10.1172/jci).  \ninsight.186938 .  \nDipeptidase-1–knockout mice develop invasive tumors with features of microsatellite-unstable colorectal cancer  \nSarah E. Glass,1,2,3 Matthew E. Bechard,2,3 Zheng Cao,2,3 Radhika Aramandla,2,3 Ping Zhao,2,3  \nSamuel T. Ellis,2,3 Emily H. Green,3,4,5 Elizabeth G. Fisher,3,6 Ryan T. Smith,2,3 Chelsie K. Sievers,2,3 Maria Johnson Irudayam,2,3 Frank Revetta,5 M. Kay Washington,5 Gregory D. Ayers,7  \nCody N. Heiser,3,8 Alan J. Simmons,1,3 Yanwen Xu,1,3 Yu Wang,7,9 Annika Windon,10  \nMartha J. Shrubsole,2,11 Nicholas O. Markham,2,3,4,5,6,12 Qi Liu,7,9 Ken S. Lau,1,3,8,13 and Robert J. Coffey1,2,3 1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 2Department of Medicine, 3Epithelial Biology Center, 4Vanderbilt Institute for Infection, Microbiology, and Immunology, and 5Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 6Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 7Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 8Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee, USA. 9Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 10Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, New York, USA. 11Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 12Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, Tennessee, USA. 13Center for Computational Systems Biology, Vanderbilt University, Nashville, Tennessee, USA.  \nDipeptidase-1 (DPEP1) is highly upregulated in colorectal cancer (CRC), with its enzymatic function linked to invasion and metastasis. More recently, DPEP1 was found to serve as a receptor for neutrophils when expressed by activated endothelial cells. It is unknown whether neutrophils bind to DPEP1-expressing CRC cells and whether this impacts features of CRC. Neutrophils have been shown to be tumor promoting in cancers including CRC, where they act to exclude CD8+ T cells. Herein, we show that neutrophils bind DPEP1-expressing CRC cells. In addition, DPEP1 is preferentially expressed in microsatellite-stable (MSS) CRCs, in which there are a paucity of CD8+ T cells, whereas DPEP1 is negatively correlated with microsatellite-unstable (MSI-H) CRCs, which are T cell rich and are more responsive to immunotherapy. Remarkably, carcinogen-treated Dpep1-null mice develop multiple, large, plaque-like, locally invasive adenocarcinomas and squamous cell cancers in the distal colon. These adenocarcinomas exhibit a marked reduction in neutrophils and an influx CD8+ T cells, along with reduced expression of mismatch repair proteins, consistent with features of MSI-H CRC. These results establish DPEP1’s importance in maintaining MSS CRC and its ability to shape the tumor microenvironment.  \nIntroduction  \nColorectal cancer (CRC), which accounts for almost 10% of cancer-related deaths in the world, has been well studied in the context of genetic changes that drive the normal epithelium toward a carcinoma (1) . Seminal work by Eric Fearon and Bert Vogelstein outlined a stepwise accumulation of genetic events that leads to CRC (2) . To identify candidate biomarkers and therapeutic targets, Vogelstein and ","cbCaigcpuQ1tZsjJ","https://ap.wps.com/l/cbCaigcpuQ1tZsjJ","pdf",30724589,18,"English","# Introduction\n## DPEP1 in colorectal cancer\n## Neutrophils, immune infiltration, and MSI-H biology","[{\"question\":\"What is the main role proposed for Dipeptidase-1 (DPEP1) in colorectal cancer?\",\"answer\":\"DPEP1 is highly upregulated in CRC and is linked to invasion and metastasis. The study further explores DPEP1 as a receptor involved in shaping interactions with neutrophils and the tumor microenvironment.\"},{\"question\":\"Do neutrophils bind to DPEP1-expressing colorectal cancer cells?\",\"answer\":\"Yes. The study shows that neutrophils bind DPEP1-expressing CRC cells, supporting a direct connection between DPEP1 expression and neutrophil engagement.\"},{\"question\":\"How does DPEP1 expression relate to microsatellite stability and immune infiltration?\",\"answer\":\"DPEP1 is preferentially expressed in microsatellite-stable (MSS) CRCs, which show fewer CD8+ T cells, and it is negatively correlated with microsatellite-unstable (MSI-H) CRCs, which are T cell rich and more responsive to immunotherapy.\"}]","Dipeptidase-1–knockout mice develop invasive tumors with features of microsatellite-unstable colorectal cancer | PDF",1790194453,45]