[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-381910-105":59,"doc-detail-381910-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","an-hgf-dependent-positive-feedback-loop-between-bladder-cancer-cells-and-fibroblasts-mediates-lymphangiogenesis-and-lymphatic-metastasis","An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis","","Cancer-associated fibroblasts (CAFs) accelerate tumor progression through reciprocal interactions with cancer cells, and tumor-derived extracellular vesicles (EVs) are central mediators of this crosstalk. The mechanisms by which tumor-derived EVs induce a CAF phenotype that drives lymph node (LN) metastasis in bladder cancer (BCa) remain insufficiently defined. This study investigates tumor-derived EV regulation of the CAF phenotype and the molecular pathways governing BCa LN metastasis.",{"@graph":69,"@context":123},[70,84,106],{"@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/an-hgf-dependent-positive-feedback-loop-between-bladder-cancer-cells-and-fibroblasts-mediates-lymphangiogenesis-and-lymphatic-metastasis/381910/",{"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/an-hgf-dependent-positive-feedback-loop-between-bladder-cancer-cells-and-fibroblasts-mediates-lymphangiogenesis-and-lymphatic-metastasis/381910.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What study question does the work address?","Question",{"text":113,"@type":114},"The study examines how tumor-derived extracellular vesicles regulate the CAF phenotype to drive lymph node metastasis in bladder cancer and investigates the underlying molecular mechanisms.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were key molecular components identified?",{"text":118,"@type":114},"High-throughput sequencing was used to identify crucial long non-coding RNAs (lncRNAs) associated with CAF enrichment in bladder cancer.",{"name":120,"@type":111,"acceptedAnswer":121},"What experimental approaches were used to test mechanisms?",{"text":122,"@type":114},"In vitro and in vivo assays assessed fibroblast-to-CAF transitions, while chromatin isolation by RNA purification, FRET, cytokine profiling, and patient-derived xenograft (PDX) models explored LINC00665-related pathways.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},381910,1790369229,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","DOI: 10.1002/cac2.12470  \nORIGINAL ARTICLE  \nAn HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis  \nYuting Li1 Yao Kong4  \nHanhao Zheng2, 3  Yuming Luo4 Yue Zhao5  YinaYin1  Le Ai1  \nYan Lin2, 3  Mingjie An2, 3 Jian Huang2, 3   \nChanghao Chen2, 3   \n1 Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China  \n2 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China  \n3 Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China  \n4 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P. R. China  \n5 Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P. R. China  \nCorrespondence  \nChanghao Chen, M.D., Ph.D. Department of Urology, Sun Yat-sen Memorial Hospital, 107 Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong 510120, P. R. China.  \nEmail: [chenchh53@mail.sysu.edu.cn](chenchh53@mail.sysu.edu.cn)  \nAbstract  \nBackground: Cancer-associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor-derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the  \nAbbreviations: CAFs, Cancer-associated fibroblasts; EVs, extracellular vesicles; LN, lymph node; BCa, bladder cancer; lncRNAs, long non-coding RNAs; PDX, patient-derived xenograft; MIBC, muscle-invasive bladder cancer; TME, tumor microenvironment; NATs, normal adjacent tissues; OS, overall survival; DFS, disease-free survival; ATCC, American Type Culture Collection; RPMI, Roswell Park Memorial Institute; MEM, minimal essential medium; HLECs, human lymphatic endothelial cells; ECM, endothelial cell medium; FBS, fetal bovine serum; CM, culture media; STR, short tandem repeat; RACE, 5’ and 3’ rapid amplification ofcDNA ends; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; α-SMA,  \nalpha-Smooth Muscle Actin; FAP, fibroblast activation protein; PDGFRα, platelet-derived growth factor receptor-α; FSC-A, forward-scatter area; SSC-A, side-scatter area; FACS, fluorescence-activated cell sorting; DTT, dithiothreitol; ROC, receiver operating characteristic; BSA, bovine serum albumin; GFP, green fluorescent protein; IHC, immunohistochemistry; NSG, nonobese diabetic/severe combined immunodeficiency/  \ninterleukin-2r-γ-null; αHGF, neutralizing antibody against hepatocyte growth factor; FRET, fluorescence resonance energy transfer; CD, circular dichroism; TFOs, triplex-forming oligonucleotides; TTS, triplex target sites; TAMRA, tetramethyl-rhodamine; FAM, fluorescein amidite; TCGA, The Cancer Genome Atlas; GEPIA, Gene Expression Profiling Interactive Analysis; hnRNPL, heterogeneous nuclear ribonucleoprotein L; SPSS, Statistical Product and Service Solutions; SD, standard deviations; χ2 test, chi-square test; ANOVA, 1-way analysis of variance; scRNA-seq, single-cell RNA sequencing; LYVE-1, lymphatic vessel endothelial hyaluronan receptor 1; MLD, micro-lymphatic vessel density; ISH, in situ hybridization; FISH, fluorescence in situ hybridization; qRT-PCR, quantitative real-time PCR; siRNA, small interfering RNA; MS, Mass spectrometry; RIP, RNA immunoprecipitation; ChIRP, chromatin isolation by RNA purification; H3K4me3, H3K4 trimethylation; ChIP, chromatin immunoprecipitation; LINC00665KO , LINC00665 knockout; LINC00665WT , LINC00665 wild type; CAFsLINC00665-EVs , LINC00665-induced EVs; IL-6, interleukin 6; IL-8, interleukin 8; Dkk-1, dickkopfWNT signaling pathway inhibitor 1; CXCL10, C-X-C motif chemokine ligand 10; VEGF, vascular endothelial growth factor; ELISA, enzyme-linked immunosorbent assay; GEO, G","cbCaimkuhPOc9sOU","https://ap.wps.com/l/cbCaimkuhPOc9sOU","pdf",14552598,23,"English","# Abstract\n## Background\n## Methods\n## Results\n## Abbreviations","[{\"question\":\"What study question does the work address?\",\"answer\":\"The study examines how tumor-derived extracellular vesicles regulate the CAF phenotype to drive lymph node metastasis in bladder cancer and investigates the underlying molecular mechanisms.\"},{\"question\":\"How were key molecular components identified?\",\"answer\":\"High-throughput sequencing was used to identify crucial long non-coding RNAs (lncRNAs) associated with CAF enrichment in bladder cancer.\"},{\"question\":\"What experimental approaches were used to test mechanisms?\",\"answer\":\"In vitro and in vivo assays assessed fibroblast-to-CAF transitions, while chromatin isolation by RNA purification, FRET, cytokine profiling, and patient-derived xenograft (PDX) models explored LINC00665-related pathways.\"}]","An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis | PDF",1790247719,58]