Academic Journal
Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK–induced cancer cell plasticity
| العنوان: | Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK–induced cancer cell plasticity |
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| المؤلفون: | Peyvandi, Sanam, Bulliard, Manon, Yilmaz, Alev, Kauzlaric, Annamaria, Marcone, Rachel, Haerri, Lisa, Coquoz, Oriana, Huang, Yu Ting, Duffey, Nathalie, Gafner, Laetitia, Lorusso, Girieca, Fournier, Nadine, Lan, Qiang, Rüegg, Curzio |
| المساهمون: | Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE |
| بيانات النشر: | AMERICAN SOCIETY FOR CLINICAL INVESTIGATION |
| سنة النشر: | 2024 |
| المجموعة: | Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: | Biochemistry, cell and molecular biology |
| الوصف: | Cancer cell plasticity contributes to therapy resistance and metastasis, which represent the main causes of cancer-related death, including in breast cancer. The tumor microenvironment drives cancer cell plasticity and metastasis, and unraveling the underlying cues may provide novel strategies for managing metastatic disease. Using breast cancer experimental models and transcriptomic analyses, we show that stem cell antigen-1 positive (SCA1+) murine breast cancer cells enriched during tumor progression and metastasis had higher in vitro cancer stem cell–like properties, enhanced in vivo metastatic ability, and generated tumors rich in Gr1hiLy6G+CD11b+ cells. In turn, tumor-educated Gr1+CD11b+ (Tu-Gr1+CD11b+) cells rapidly and transiently converted low metastatic SCA1– cells into highly metastatic SCA1+ cells via secreted oncostatin M (OSM) and IL-6. JAK inhibition prevented OSM/IL-6–induced SCA1+ population enrichment, while OSM/IL-6 depletion suppressed Tu-Gr1+CD11b+–induced SCA1+ population enrichment in vitro and metastasis in vivo. Moreover, chemotherapy-selected highly metastatic 4T1 cells maintained high SCA1+ positivity through autocrine IL-6 production, and in vitro JAK inhibition blunted SCA1 positivity and metastatic capacity. Importantly, Tu-Gr1+CD11b+ cells invoked a gene signature in tumor cells predicting shorter overall survival (OS), relapse-free survival (RFS), and lung metastasis in breast cancer patients. Collectively, our data identified OSM/IL-6/JAK as a clinically relevant paracrine/autocrine axis instigating breast cancer cell plasticity and triggering metastasis. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | The authors wish to thank Sarah Cattin and Melissa Rizzo for assistance with FACS analysis, Ana-Marija Sulić (Institute of Biotechnology, HiLIFE, University of Helsinki) for the insightful discussion about scRNA-Seq data analysis, CSC – IT Center for Science, Finland, for computational resources, Fred R. Miller (Michigan Cancer Foundation, Detroit, Michigan, USA) for providing 4T1 cells, and Khalil Zaman (Department of Oncology, University Hospital, University of Lausanne, Lausanne, Switzerland) for providing chemotherapeutic drugs. This work was supported by grants from the Swiss National Science Foundation (31003A_179248; 310030_208136), the Swiss Cancer League (KFS 4400-02-2018), and the Medic Foundation (to CR). Illustrative schemes were created with BioRender.com.; Peyvandi , S , Bulliard , M , Yilmaz , A , Kauzlaric , A , Marcone , R , Haerri , L , Coquoz , O , Huang , Y T , Duffey , N , Gafner , L , Lorusso , G , Fournier , N , Lan , Q & Rüegg , C 2024 , ' Tumor-educated Gr1 + CD11b + cells drive breast cancer metastasis via OSM/IL-6/JAK–induced cancer cell plasticity ' , Journal of Clinical Investigation , vol. 134 , no. 6 , e166847 . https://doi.org/10.1172/JCI166847; ORCID: /0000-0002-7765-6767/work/159904016; http://hdl.handle.net/10138/575585; a2d45f9d-b210-4d20-b105-a2c0d0b63420; 85187959796 |
| الاتاحة: | http://hdl.handle.net/10138/575585 |
| Rights: | cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: | edsbas.1A3AC50 |
| قاعدة البيانات: | BASE |
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