[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329808-105":59,"doc-detail-329808-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","profiling-the-cancer-prone-microenvironment-in-a-zebrafish-model-for-mpnst","Profiling the cancer-prone microenvironment in a zebrafish model for MPNST","","The tumor microenvironment shapes cancer cell survival, growth, invasion, and metastasis, yet the precancerous microenvironment and its interactions with incipient cancer cells remain difficult to define. A zebrafish model was developed to separate microenvironmental, precancerous, and cancer cell populations by fluorescence-activated cell sorting. RNA-seq revealed broadly activated inflammation/immune signaling, stage-specific gene expression transitions, and macrophage-associated microenvironment phenotypes. Comparative genomics identified conserved changes in MPNST versus benign lesions across humans and zebrafish, and functional validation confirmed periostin (POSTN) in human MPNST.",{"@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/profiling-the-cancer-prone-microenvironment-in-a-zebrafish-model-for-mpnst/329808/",{"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/profiling-the-cancer-prone-microenvironment-in-a-zebrafish-model-for-mpnst/329808.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the precancerous microenvironment important for cancer initiation?","Question",{"text":112,"@type":113},"The precancerous microenvironment is proposed to be equally important during cancer initiation, but specific interactions during cancer onset are challenging to characterize.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the zebrafish model enable separation of cell populations?",{"text":117,"@type":113},"It uses fluorescence-activated cell sorting with a reporter construct to partition microenvironmental, precancerous, and cancer cell populations into mutually exclusive groups.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the RNA-seq analyses show about signaling and immune involvement?",{"text":121,"@type":113},"RNA-seq demonstrated broad activation of inflammation and immune-associated signaling networks and identified gene expression patterns distinguishing cancer from precancerous microenvironments.","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},329808,1791071305,{"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":34,"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,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1794309523707217728","Oncogene [www.nature.com/onc](www.nature.com/onc)  \nARTICLE OPEN   \nProfiling the cancer-prone microenvironment in a zebrafish model for MPNST  \nCheryl Cero 1,2,9, John S. House 3,9, Vincenzo Verdi 1, Jordan L. Ferguson4, Dereje D. Jima5, Aubrie A. Selmek6, Olivia M. Patania7, Jennifer E. Dwyer1, Bih-Rong Wei1, Dillon T. Lloyd3,8 and Heather R. Shive 1,6 ✉  \nThis is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024  \n\n|  | Microenvironmental contributions to soft tissue sarcoma progression are relatively undefined, particularly during sarcoma onset. Use of animal models to reveal these contributions is impeded by difficulties in discriminating between microenvironmental, precancerous, and cancer cells, and challenges in defining a precancerous microenvironment. We developed a zebrafish model that allows segregation of microenvironmental, precancerous, and cancerous cell populations by fluorescence-activated cell sorting. This model has high predilection for malignant peripheral nerve sheath tumor (MPNST), a type of soft tissue sarcoma that exhibits rapid, aggressive growth. Using RNA-seq, we profiled the transcriptomes of microenvironmental, precancerous, and cancer cells from our zebrafish MPNST model. We show broad activation of inflammation/immune-associated signaling networks, describe gene expression patterns that uniquely characterize the transition from precancerous to cancer ME, and identify macrophages as potential contributors to microenvironmental phenotypes. We identify conserved gene expression changes and candidate genes of interest by comparative genomics analysis of MPNST versus benign lesions in both humans and zebrafish. Finally, we functionally validate a candidate extracellular matrix protein, periostin (POSTN), in human MPNST. This work provides insight into how the |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| microenvironment may regulate MPNST initiation and progression. |  |  |\n|  | Oncogene (2025) 44:179–191; [https://doi.org/10.1038/s41388-024-03210-1](https://doi.org/10.1038/s41388-024-03210-1) |  |\n|  |  |  |\n\nINTRODUCTION  \nThe tumor microenvironment directly impacts cancer cell survival, growth, invasion, and metastasis. The precancerous microenvironment is proposed to be equally important during cancer initiation [1, 2] . However, specific interactions between microenvironmental cells and incipient cancer cells during cancer onset are challenging to characterize. Furthermore, genetic and molecular events that occur during the transition from precancerous to cancer microenvironment are not defined.  \nAnimal models for heritable cancer syndromes are uniquely suited for identifying microenvironmental factors that support carcinogenesis. In these models, cancers are caused by known genetic mutations and occur in a predictable temporal and tissuespecific manner. However, use of animal models to profile the microenvironment for cancer-associated gene expression patterns necessitates a method for distinguishing microenvironmental cells from precancerous or cancer cells.  \nTo overcome this requisite, we developed a zebrafish model that enabled us to partition microenvironmental, precancerous, and cancer cell populations into mutually exclusive groups by fluorescence-activated cell sorting using a reporter construct to identify cancer cells and potential precancerous cells. This model exhibits high predilection for malignant peripheral nerve sheath  \ntumor (MPNST) [3], a type of soft tissue sarcoma with a particularly poor prognosis due to aggressive growth, limited response to conventional treatment, and ineffective targeted therapies [4–7] . In our model, MPNST is caused by combined heritable mutations in the tumor suppressor genes TP53 and BRCA2 [8–10] . MPNSTs in this model preferentially arise in a discrete anatomic location within a predictable timeframe [9, 10], ","cbCaioC924igAou9","https://ap.wps.com/l/cbCaioC924igAou9","pdf",6968095,13,"English","# Introduction\n## Tumor microenvironment and the precancerous niche\n## Zebrafish model design for cell-state segregation\n## Transcriptomic profiling and immune-associated findings","[{\"question\":\"Why is the precancerous microenvironment important for cancer initiation?\",\"answer\":\"The precancerous microenvironment is proposed to be equally important during cancer initiation, but specific interactions during cancer onset are challenging to characterize.\"},{\"question\":\"How does the zebrafish model enable separation of cell populations?\",\"answer\":\"It uses fluorescence-activated cell sorting with a reporter construct to partition microenvironmental, precancerous, and cancer cell populations into mutually exclusive groups.\"},{\"question\":\"What did the RNA-seq analyses show about signaling and immune involvement?\",\"answer\":\"RNA-seq demonstrated broad activation of inflammation and immune-associated signaling networks and identified gene expression patterns distinguishing cancer from precancerous microenvironments.\"}]","Profiling the cancer-prone microenvironment in a zebrafish model for MPNST | PDF",1789985690,33]