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In prostate cancer, CAFs promote malignancy through metabolic rewiring, including glutamine metabolism. A co-culture model using colour-labelled prostate cancer cells and fibroblasts tests CAF impact on proliferation and clonogenicity, complemented by glutamine deprivation, GLS1 inhibition, proteomics, and patient tissue analyses. Elevated GLS1 in epithelium and stroma correlates with a high-risk subgroup potentially benefiting from GLS1-targeted therapies.",{"@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/prostate-cancers-silent-partners-fibroblasts-and-their-influence-on-glutamine-metabolism-manipulation/328895/",{"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/prostate-cancers-silent-partners-fibroblasts-and-their-influence-on-glutamine-metabolism-manipulation/328895.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","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},"What role do cancer-associated fibroblasts play in prostate cancer progression?","Question",{"text":112,"@type":113},"CAFs are pro-tumorigenic fibroblasts that remodel the tumour microenvironment, promote communication with cancer cells and immune infiltrates, and support metabolic rewiring that contributes to progression and therapy response.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study test whether CAFs influence prostate cancer growth?",{"text":117,"@type":113},"The study used a co-culture system with colour-labelled prostate cancer cell lines and fibroblasts to measure effects on proliferation and clonogenic potential.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is GLS1 considered a potential therapeutic target?",{"text":121,"@type":113},"Experiments showed that increased growth in hormone-sensitive cells is linked to glutamine dependence, and patient tissue analysis revealed elevated GLS1 in both prostate cancer epithelium and stroma, identifying a high-risk group that may benefit from GLS1-targeted therapies.","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},328895,1790015004,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"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},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Article  \nProstate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation  \nPia V. Hönscheid 1,2,3, Gustavo B. Baretton 1,2,3,4, Martin Puhr 5, Tiziana Siciliano 1,6, Justus S. Israel 6,  \nMatthias B. Stope 7,8, Celina Ebersbach 6, Alicia-Marie K. Beier 6, Christian Thomas 3,6 and Holger H. H. Erb 6,8, *  \nCitation: Hönscheid, P.V.; Baretton, G.B.; Puhr, M.; Siciliano, T.; Israel, J.S.; Stope, M.B.; Ebersbach, C.; Beier, A.-M.K.; Thomas, C.; Erb, H.H.H. Prostate Cancer’s Silent Partners:  \nFibroblasts and Their Influence on Glutamine Metabolism Manipulation. Int. J. Mol. Sci. 2024, 25, 9275. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25179275](doi.org/10.3390/ijms25179275)  \nAcademic Editors: Maria Concetta Faniello and Maria Mesuraca  \nReceived: 4 August 2024  \nRevised: 24 August 2024  \nAccepted: 25 August 2024  \nPublished: 27 August 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany; pia.hoenscheid@ukdd.de (P.V.H.);  \ngustavo.baretton@uniklinikum-dresden.de (G.B.B.); tiziana.siciliano@uniklinikum-dresden.de (T.S.)  \n2 Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT) Dresden, 01307 Dresden, Germany  \n3 National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany;  \nchristian.thomas@uniklinikum-dresden.de  \n4 Tumor and Normal Tissue Bank of the University Cancer Center (UCC), University Hospital Carl Gustav Carus, Medical Faculty, TU Dresden, 01307 Dresden, Germany  \n5 Department of Urology, Medical University of Innsbruck, 6020 Innsbruck, Austria; [martin.puhr@i-med.ac.at](martin.puhr@i-med.ac.at)  \n6 Department of Urology, University Hospital Carl Gustav Carus, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany; justussimon.israel@uniklinikum-dresden.de (J.S.I.);  \ncelina.ebersbach@uniklinikum-dresden.de (C.E.); aliciamarie.beier@uniklinikum-dresden.de (A.-M.K.B.)  \n7 Department of Gynecology and Gynecological Oncology, University Hospital Bonn, 53127 Bonn, Germany; [matthias.stope@ukbonn.de](matthias.stope@ukbonn.de)  \n8 UroFors Consortium (Natural Scientists in Urological Research), German Society of Urology,  \n14163 Berlin, Germany  \n* Correspondence: holger.erb@uniklinikum-dresden.de; Tel.: +49-(0)351-458-13597  \nAbstract: Cancer-associated fibroblast (CAF)s in the tumour microenvironment (TME) modulate the extracellular matrix, interact with cancer cells, and facilitate communication with infiltrating leukocytes, significantly contributing to cancer progression and therapeutic response. In prostate cancer (PCa), CAFs promote malignancy through metabolic rewiring, cancer stem cell regulation, and therapy resistance. Pre-clinical studies indicate that targeting amino acid metabolism, particularly glutamine (Gln) metabolism, reduces cancer proliferation and stemness. However, most studies lack the context of CAF–cancer interaction, focusing on monocultures. This study assesses the influence of CAFs on PCa growth by manipulating Gln metabolism using colour-labelled PCa cell lines (red) and fibroblast (green) in a co-culture system to evaluate CAFs’ effects on PCa cell proliferation and clonogenic potential. CAFs increased the proliferation of hormone-sensitive LNCaP cells, whereas the castration-resistant C4-2 cells were unaffected. However, clonogenic growth increased in both cell lines. Gln deprivation and GLS1 inhibition experiments revealed that the increased growth rate of LNCAP cells was associated with increased dependence on Gln, which was confirmed ","cbCaivRWbl4UHVCH","https://ap.wps.com/l/cbCaivRWbl4UHVCH","pdf",3027879,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What role do cancer-associated fibroblasts play in prostate cancer progression?\",\"answer\":\"CAFs are pro-tumorigenic fibroblasts that remodel the tumour microenvironment, promote communication with cancer cells and immune infiltrates, and support metabolic rewiring that contributes to progression and therapy response.\"},{\"question\":\"How did the study test whether CAFs influence prostate cancer growth?\",\"answer\":\"The study used a co-culture system with colour-labelled prostate cancer cell lines and fibroblasts to measure effects on proliferation and clonogenic potential.\"},{\"question\":\"Why is GLS1 considered a potential therapeutic target?\",\"answer\":\"Experiments showed that increased growth in hormone-sensitive cells is linked to glutamine dependence, and patient tissue analysis revealed elevated GLS1 in both prostate cancer epithelium and stroma, identifying a high-risk group that may benefit from GLS1-targeted therapies.\"}]","Prostate Cancer’s Silent Partners - Fibroblasts and Their Influence on Glutamine Metabolism Manipulation | PDF",1789981536,48]