[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-340312-105":59,"doc-detail-340312-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","osteopontin-is-a-therapeutic-target-that-drives-breast-cancer-recurrence-accepted-29-september-2024","Osteopontin is a therapeutic target that drives breast cancer recurrence - Accepted 29 September 2024","","Recurrent breast cancers frequently resist standard therapies, and identifying actionable drivers of relapse limits long-term improvement. This study characterizes tumor-cell derived osteopontin as an autocrine and paracrine promoter of tumor recurrence. Osteopontin enhances proliferation, recruits macrophages, and with IL-4 induces a protumorigenic macrophage polarization. Inhibition or macrophage depletion reduces recurrent tumor growth, while osteopontin targeting in mouse models blocks metastasis and improves anti-PD-1 responses. Clinically, osteopontin expression tracks with recurrence and poor prognosis.",{"@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/osteopontin-is-a-therapeutic-target-that-drives-breast-cancer-recurrence-accepted-29-september-2024/340312/",{"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/osteopontin-is-a-therapeutic-target-that-drives-breast-cancer-recurrence-accepted-29-september-2024/340312.png","ImageObject",300,407,{"name":92,"@type":93},"Skyler","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the key finding about osteopontin in recurrent breast cancer?","Question",{"text":112,"@type":113},"Tumor-cell derived osteopontin acts as an autocrine and paracrine driver of tumor recurrence, promoting progression and relapse.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does osteopontin influence the tumor microenvironment?",{"text":117,"@type":113},"Osteopontin promotes tumor proliferation, recruits macrophages, and synergizes with IL-4 to polarize macrophages toward a protumorigenic state.",{"name":119,"@type":110,"acceptedAnswer":120},"What are the effects of osteopontin inhibition in vivo?",{"text":121,"@type":113},"Macrophage depletion and osteopontin inhibition reduce recurrent tumor growth, and osteopontin targeting in primary tumor-bearing mice prevents metastasis and supports T cell infiltration and activation, improving anti-PD-1 response.","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},340312,1790824197,{"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":39,"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},2336464648746,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article [https://doi.org/10.1038/s41467-024-53023-9](https://doi.org/10.1038/s41467-024-53023-9)  \nOsteopontin is a therapeutic target that drives breast cancer recurrence  \nReceived: 5 April 2024  \n\n| Accepted: 29 September 2024 |\n| --- |\n| |\n| Check for updates |\n\nYu Gu1,2, Tarek Taifour1,3, Tung Bui1,2, Dongmei Zuo1, Alain Pacis1,4, Alexandre Poirier 1,3, Sherif Attalla1, Anne-Marie Fortier 1, Virginie Sanguin-Gendreau1, Tien-Chi Pan5, Vasilios Papavasiliou1, Nancy U. Lin 6, Melissa E. Hughes6, Kalie Smith6, Morag Park 1,2,7, Michel L. Tremblay 1,2,3,7, Lewis A. Chodosh5, Rinath Jeselsohn 6 & William J. Muller 1,2,7   \nRecurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a protumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin’s multiaxial role in breast cancer progression and recurrence.  \nCancer relapse remains the major hurdle in the clinical management of breast cancer. Local and metastatic recurrent tumors often foster therapy resistance, leading to disease lethality. During the stepwise progression ofbreast cancer, a proportion oftumor cells can enter a state of dormancy characterized by temporary cell cycle arrest before they reactivate and resume proliferation1,2. Tumor cell-intrinsic adaptations such as genetic mutations must occur to disrupt the equilibrium maintained within a dormant tumor cell3. Additionally, tumor environmental changes also contribute to shifting the balance in favor of malignant  \nprogression and recurrence3,4. Therefore, dormancy exit is a forcefully dynamic and multi-stage process orchestrated by tumor cell-intrinsic and microenvironmental drivers within a recurrent tumor.  \nGenetically engineered mouse models (GEMMs) that recapitulate key features of human disease have provided valuable insights for our understanding of the complexity of tumor microenvironmental interactions in breast cancer progression and recurrence1,5. The versatility of GEMMs has allowed us to dissect the contributions of immune cell populations that promote relapse within a recurrent  \n1Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada. 2Department of Biochemistry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. 3Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. 4Canadian Centre for Computational Genomics, McGill University Genome Center, Montreal, QC, Canada. 5Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 6Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 7Faculty of Medicine, McGill University, Montreal, QC, Canada. [e-mail:](e-mail: william.muller@mcgill.ca)[ william.muller@mcgill.ca](e-mail: william.muller@mcgill.ca)  \na  \nMIC WT MIC β1KO  \nmSpp1  \nOPN  \n+ PanCK  \n+ PanCK  \n+ DAPI  \n+ DAPI  \nb  \ne  \n3×10 5  \n2×10 5  \n1×10 5  \n0  \nc  \nMIC WT  \nSpp 1 transcrip","cbCaivrqD8d0Rgac","https://ap.wps.com/l/cbCaivrqD8d0Rgac","pdf",8680661,"English","# Abstract\n## Recurrence and therapy resistance\n## Osteopontin as a driver of recurrence\n## Macrophage recruitment and IL-4 synergy\n## Effects of osteopontin inhibition\n## Evidence from clinical correlation and mouse models","[{\"question\":\"What is the key finding about osteopontin in recurrent breast cancer?\",\"answer\":\"Tumor-cell derived osteopontin acts as an autocrine and paracrine driver of tumor recurrence, promoting progression and relapse.\"},{\"question\":\"How does osteopontin influence the tumor microenvironment?\",\"answer\":\"Osteopontin promotes tumor proliferation, recruits macrophages, and synergizes with IL-4 to polarize macrophages toward a protumorigenic state.\"},{\"question\":\"What are the effects of osteopontin inhibition in vivo?\",\"answer\":\"Macrophage depletion and osteopontin inhibition reduce recurrent tumor growth, and osteopontin targeting in primary tumor-bearing mice prevents metastasis and supports T cell infiltration and activation, improving anti-PD-1 response.\"}]","Osteopontin is a therapeutic target that drives breast cancer recurrence - Accepted 29 September 2024 | PDF",1790035722,48]