{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:19:02Z","timestamp":1790356742391,"version":"4.1.0"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Breast cancer is a leading cause of cancer-related mortality among women, with nearly 70% of cases being estrogen receptor-positive (ER+). While endocrine therapies, such as tamoxifen, have significantly improved patient outcomes, resistance\u2014whether intrinsic or acquired\u2014remains a major clinical challenge that limits treatment efficacy. Emerging evidence suggests that endocrine resistance is often driven by the presence and expansion of cancer stem cells (CSCs), which contribute to recurrence, metastasis, and therapeutic failure. The tumor microenvironment (TME), including immune cells like macrophages, soluble factors, and extracellular vesicles (EVs), plays a crucial role in promoting tumor progression and therapy resistance. EVs are small lipid bilayer-bound particles that facilitate intercellular communication by transferring bioactive cargo capable of reprogramming recipient cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the role of macrophage-derived EVs in endocrine resistance, we isolated EVs from TNF-\u03b1-conditioned macrophages (TNF EVs) and treated MCF-7 ER+ breast cancer cells with these vesicles. We assessed changes in proliferation, migration, epithelial-mesenchymal transition (EMT), CSC-like properties, and tamoxifen resistance. Additionally, we evaluated whether tumor-derived EVs modulate macrophage polarization by analyzing the expression of PD-1 and other immunomodulatory markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TNF EV-treated MCF-7 cells showed significantly increased proliferation, enhanced migratory behavior, and morphological changes associated with EMT. Importantly, treated cells developed a stem-like phenotype, characterized by a larger CD44<jats:sup>High<\/jats:sup>\/CD24<jats:sup>Low<\/jats:sup> subpopulation and improved spheroid-forming ability. These features correlated with sustained proliferation even in the presence of tamoxifen, supporting the development of endocrine resistance. Furthermore, EVs derived from tumor cells triggered macrophage polarization toward a tumor-associated macrophage (TAM) profile, with increased PD-1 expression, indicating a role in immune suppression and tumor immune evasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings emphasize the dual role of TNF-\u03b1-conditioned macrophage-derived EVs in driving both endocrine resistance and immune modulation in ER+ breast cancer. By promoting stemness, EMT, and tamoxifen resistance, as well as inducing immunosuppressive macrophage polarization, these EVs emerge as key contributors to tumor progression. Our study highlights the therapeutic potential of targeting EV-mediated communication to overcome endocrine resistance and enhance clinical outcomes for ER+ breast cancer patients. This work establishes a critical framework for future studies aimed at harnessing EVs as therapeutic targets or biomarkers in breast cancer management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1548724","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:53:14Z","timestamp":1749714794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Intercellular communication between extracellular vesicles from conditioned macrophages and breast cancer cells drives endocrine therapy resistance"],"prefix":"10.3389","volume":"13","author":[{"given":"Mar\u00eda C.","family":"Rodriguez-Baili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Palma-Cobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar G.","family":"Prucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Y\u00e1\u00f1ez-M\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German A.","family":"Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/jcb.21318","article-title":"The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells","volume":"102","author":"Abache","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.3390\/molecules25153355","article-title":"Tamoxifen and the PI3K inhibitor: LY294002 synergistically induce apoptosis and cell cycle arrest in breast cancer MCF-7 cells","volume":"25","author":"Abdallah","year":"2020","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"eaal3604","DOI":"10.1126\/scitranslmed.aal3604","article-title":"In vivo imaging reveals a tumor-associated macrophage mediated resistance pathway in anti-PD-1 therapy","volume":"9","author":"Arlauckas","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2300062","DOI":"10.1002\/pmic.202300062","article-title":"Extracellular vesicle proteins as breast cancer biomarkers: mass spectrometry-based analysis","volume":"24","author":"Bandu","year":"2024","journal-title":"PROTEOMICS"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.02.013","article-title":"Biogenesis and function of extracellular vesicles in cancer","volume":"188","author":"Bebelman","year":"2018","journal-title":"Pharmacol. and Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature03096","article-title":"Stromal fibroblasts in cancer initiation and progression","volume":"432","author":"Bhowmick","year":"2004","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/path.1027","article-title":"The role of tumour\u2010associated macrophages in tumour progression: implications for new anticancer therapies","volume":"196","author":"Bingle","year":"2002","journal-title":"J. Pathology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.ccell.2021.02.013","article-title":"Progressive immune dysfunction with advancing disease stage in renal cell carcinoma","volume":"39","author":"Braun","year":"2021","journal-title":"Cancer Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41577-022-00763-8","article-title":"The roles of extracellular vesicles in the immune system","volume":"23","author":"Buzas","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1093\/intimm\/dxh267","article-title":"Exosomal-like vesicles are present in human blood plasma","volume":"17","author":"Caby","year":"2005","journal-title":"Int. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3390\/cancers11020189","article-title":"Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells","volume":"11","author":"Castellaro","year":"2019","journal-title":"Cancers"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3462","DOI":"10.1158\/1078-0432.CCR-13-0855","article-title":"PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies","volume":"19","author":"Chen","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4236\/jct.2022.133009","article-title":"Breast cancer MCF-7 cell spheroid culture for drug discovery and development","volume":"13","author":"Chen","year":"2022","journal-title":"J. Cancer Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1007\/s13277-013-1417-4","article-title":"MicroRNAs delivered by extracellular vesicles: an emerging resistance mechanism for breast cancer","volume":"35","author":"Chen","year":"2014","journal-title":"Tumor Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"6834","DOI":"10.3390\/ijms24076834","article-title":"A basic review on estrogen receptor signaling pathways in breast cancer","volume":"24","author":"Clusan","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.cell.2020.04.054","article-title":"SnapShot: extracellular vesicles","volume":"182","author":"Cocozza","year":"2020","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5553","DOI":"10.1242\/jcs.128868","article-title":"Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles","volume":"126","author":"Colombo","year":"2013","journal-title":"J. Cell Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5338","DOI":"10.3390\/ijms14035338","article-title":"Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications","volume":"14","author":"Corrado","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e12144","DOI":"10.1002\/jev2.12144","article-title":"A brief history of nearly EV\u2010erything \u2013 the rise and rise of extracellular vesicles","volume":"10","author":"Couch","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"B21","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1126\/science.1232227","article-title":"Neutralizing tumor-promoting chronic inflammation: a magic bullet?","volume":"339","author":"Coussens","year":"2013","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13402-019-00489-1","article-title":"The dual role of tumor necrosis factor-alpha (TNF-\u03b1) in breast cancer: molecular insights and therapeutic approaches","volume":"43","author":"Cruceriu","year":"2020","journal-title":"Cell Oncol. (Dordr)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1074\/mcp.M112.022806","article-title":"Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS","volume":"12","author":"Demory","year":"2013","journal-title":"Mol. Cell Proteomics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3322\/caac.21583","article-title":"Breast cancer statistics, 2019","volume":"69","author":"DeSantis","year":"2019","journal-title":"CA. Cancer. J. Clin."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e12419","DOI":"10.1002\/jev2.12419","article-title":"Extracellular vesicles as a promising source of lipid biomarkers for breast cancer detection in blood plasma","volume":"13","author":"Dorado","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"B26","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/bcr3037","article-title":"Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity","volume":"13","author":"Drasin","year":"2011","journal-title":"Breast Cancer Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1158\/0008-5472.CAN-07-5704","article-title":"Anti\u2013tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis","volume":"68","author":"Egberts","year":"2008","journal-title":"Cancer Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s12032-024-02423-4","article-title":"A study with cancer stem cells and three-dimensional tumoroids: investigation of the combined effects of 5-fluorouracil and doxorubicin in breast cancer","volume":"41","author":"Erden Tayhan","year":"2024","journal-title":"Med. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e20191869","DOI":"10.1084\/jem.20191869","article-title":"Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer","volume":"217","author":"Etzerodt","year":"2020","journal-title":"J. Exp. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40425-017-0240-7","article-title":"Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer","volume":"5","author":"Fortis","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1186\/s12885-015-1546-9","article-title":"M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide","volume":"15","author":"Genin","year":"2015","journal-title":"BMC Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.scr.2016.02.028","article-title":"CD44highCD24low molecular signature determines the cancer stem cell and EMT phenotype in oral squamous cell carcinoma","volume":"16","author":"Ghuwalewala","year":"2016","journal-title":"Stem Cell Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nature22396","article-title":"PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity","volume":"545","author":"Gordon","year":"2017","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ccell.2020.03.009","article-title":"Overcoming endocrine resistance in breast cancer","volume":"37","author":"Hanker","year":"2020","journal-title":"Cancer Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"10961","DOI":"10.1038\/s41598-019-47375-2","article-title":"Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer","volume":"9","author":"Honkanen","year":"2019","journal-title":"Sci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"11491","DOI":"10.18632\/aging.202841","article-title":"Comprehensive analysis of ferritin subunits expression and positive correlations with tumor-associated macrophages and T regulatory cells infiltration in most solid tumors","volume":"13","author":"Hu","year":"2021","journal-title":"Aging"},{"key":"B38","doi-asserted-by":"publisher","first-page":"13993","DOI":"10.3390\/ijms232213993","article-title":"Tumor-derived exosomes and their role in breast cancer metastasis","volume":"23","author":"Huang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1158\/1078-0432.CCR-09-1823","article-title":"New strategies in estrogen receptor\u2013positive breast cancer","volume":"16","author":"Johnston","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1159\/000086950","article-title":"Tumour-stromal interactions in breast cancer: the role of stroma in tumourigenesis","volume":"26","author":"Kim","year":"2005","journal-title":"Tumor Biol."},{"key":"B41","first-page":"3703","article-title":"Purification, characterization and biological significance of tumor-derived exosomes","volume":"25","author":"Koga","year":"2005","journal-title":"Anticancer Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.addr.2015.11.009","article-title":"Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy","volume":"99","author":"Komohara","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12885-020-6629-6","article-title":"Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients","volume":"20","author":"Kono","year":"2020","journal-title":"BMC Cancer"},{"key":"B44","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1758-907X-1-7","article-title":"microRNA as a new immune-regulatory agent in breast milk","volume":"1","author":"Kosaka","year":"2010","journal-title":"Silence"},{"key":"B45","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3389\/fgene.2013.00173","article-title":"Trash or Treasure: extracellular microRNAs and cell-to-cell communication","volume":"4","author":"Kosaka","year":"2013","journal-title":"Front. Genet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/febs.15558","article-title":"Exosomes as mediators of immune regulation and immunotherapy in cancer","volume":"288","author":"Kugeratski","year":"2020","journal-title":"FEBS J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.3390\/cancers13051160","article-title":"The emerging role of extracellular vesicles in endocrine resistant breast cancer","volume":"13","author":"La Camera","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"207","DOI":"10.31083\/j.fbl2809207","article-title":"The roles and targeting of tumor-associated macrophages","volume":"28","author":"Li","year":"2023","journal-title":"FBL"},{"key":"B49","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12935-020-01659-0","article-title":"Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p","volume":"21","author":"Liu","year":"2021","journal-title":"Cancer Cell Int."},{"key":"B50","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, mechanisms, and significance of macrophage plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1919082","DOI":"10.1155\/2019\/1919082","article-title":"Beyond T cells: understanding the role of PD-1\/PD-L1 in tumor-associated macrophages","volume":"2019","author":"Lu","year":"2019","journal-title":"J. Immunol. Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12943-019-0965-7","article-title":"Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance","volume":"18","author":"Maacha","year":"2019","journal-title":"Mol. Cancer"},{"key":"B53","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","article-title":"The epithelial-mesenchymal transition generates cells with properties of stem cells","volume":"133","author":"Mani","year":"2008","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.semcdb.2015.02.010","article-title":"Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes","volume":"40","author":"Minciacchi","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"7239","DOI":"10.3390\/ijms22137239","article-title":"Tumor-associated macrophages: combination of therapies, the approach to improve cancer treatment","volume":"22","author":"Moeini","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5728","DOI":"10.1158\/0008-5472.CAN-09-4672","article-title":"Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes","volume":"70","author":"Movahedi","year":"2010","journal-title":"Cancer Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/j.cub.2009.09.059","article-title":"ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles","volume":"19","author":"Muralidharan-Chari","year":"2009","journal-title":"Curr. Biol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.pharmthera.2016.03.013","article-title":"Three-dimensional culture systems in cancer research: focus on tumor spheroid model","volume":"163","author":"Nath","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"B60","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.3390\/cancers15194846","article-title":"Three-Dimensional in vitro tumor spheroid models for evaluation of anticancer therapy: recent updates","volume":"15","author":"Nayak","year":"2023","journal-title":"Cancers"},{"key":"B61","doi-asserted-by":"publisher","first-page":"22164","DOI":"10.1038\/s41598-023-48279-y","article-title":"Morphological and cytoskeleton changes in cells after EMT","volume":"13","author":"Nurmagambetova","year":"2023","journal-title":"Sci. Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s12672-011-0066-6","article-title":"Breast cancer stem cells and their role in resistance to endocrine therapy","volume":"2","author":"O\u2019Brien","year":"2011","journal-title":"Horm. CANC"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1016\/j.ejca.2013.01.017","article-title":"Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells","volume":"49","author":"O\u2019Brien","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"B64","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s12282-024-01563-9","article-title":"Prospects for liquid biopsy using microRNA and extracellular vesicles in breast cancer","volume":"32","author":"Ochiya","year":"2024","journal-title":"Breast Cancer"},{"key":"B65","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ncb2000","article-title":"Rab27a and Rab27b control different steps of the exosome secretion pathway","volume":"12","author":"Ostrowski","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e8577","DOI":"10.1371\/journal.pone.0008577","article-title":"Nanostructural and transcriptomic analyses of human saliva derived exosomes","volume":"5","author":"Palanisamy","year":"2010","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1615\/critreveukargeneexpr.v20.i2.10","article-title":"Tumor necrosis factor-\u03b1 signaling in macrophages","volume":"20","author":"Parameswaran","year":"2010","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"B68","doi-asserted-by":"publisher","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/pros.20860","article-title":"Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen","volume":"69","author":"Poliakov","year":"2009","journal-title":"Prostate"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.yexcr.2008.09.020","article-title":"Trafficking and function of the tetraspanin CD63","volume":"315","author":"Pols","year":"2009","journal-title":"Exp. Cell Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e42899","DOI":"10.7759\/cureus.42899","article-title":"Utility of CD44\/CD24 in the outcome and prognosis of oral squamous cell carcinoma: a systematic review","volume":"15","author":"Poothakulath Krishnan","year":"2023","journal-title":"Cureus"},{"key":"B72","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.1128\/mcb.18.8.4499","article-title":"c-Myc or Cyclin D1 mimics estrogen effects on Cyclin E-cdk2 activation and cell cycle reentry","volume":"18","author":"Prall","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/bies.201100169","article-title":"Extracellular vesicles--vehicles that spread cancer genes","volume":"34","author":"Rak","year":"2012","journal-title":"Bioessays"},{"key":"B74","doi-asserted-by":"publisher","first-page":"12347","DOI":"10.3390\/s120912347","article-title":"Multiple applications of alamar blue as an indicator of metabolic function and cellular health in cell viability bioassays","volume":"12","author":"Rampersad","year":"2012","journal-title":"Sensors"},{"key":"B75","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3389\/fendo.2019.00245","article-title":"Endocrine resistance in hormone receptor positive breast cancer-from mechanism to therapy","volume":"10","author":"Rani","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","article-title":"B lymphocytes secrete antigen-presenting vesicles","volume":"183","author":"Raposo","year":"1996","journal-title":"J. Exp. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.3390\/cancers11071028","article-title":"The central contributions of breast cancer stem cells in developing resistance to endocrine therapy in estrogen receptor (ER)-Positive breast cancer","volume":"11","author":"Rodriguez","year":"2019","journal-title":"Cancers"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.febslet.2013.03.012","article-title":"Identification and characterization of the nano-sized vesicles released by muscle cells","volume":"587","author":"Romancino","year":"2013","journal-title":"FEBS Lett."},{"key":"B79","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/s0960-0760(03)00037-2","article-title":"Effect of tamoxifen and 2-methoxyestradiol alone and in combination on human breast cancer cell proliferation","volume":"84","author":"Seeger","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3390\/molecules23040829","article-title":"Krasil\u2019nikov MA: exosome-mediated transfer of cancer cell resistance to antiestrogen drugs","volume":"23","author":"Semina","year":"2018","journal-title":"Mol. A J. Synthetic Chem. Nat. Prod. Chem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"5094","DOI":"10.2741\/3066","article-title":"TNF: a master switch for inflammation to cancer","volume":"13","author":"Sethi","year":"2008","journal-title":"FBL"},{"key":"B82","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.ejmech.2017.11.056","article-title":"Tamoxifen a pioneering drug: an update on the therapeutic potential of tamoxifen derivatives","volume":"143","author":"Shagufta","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"B83","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/mc.23277","article-title":"Breast cancer stem cells: a review of their characteristics and the agents that affect them","volume":"60","author":"Shan","year":"2021","journal-title":"Mol. Carcinog."},{"key":"B84","doi-asserted-by":"publisher","first-page":"R59","DOI":"10.1186\/bcr1610","article-title":"CD44+\/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis","volume":"8","author":"Sheridan","year":"2006","journal-title":"Breast Cancer Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"9825","DOI":"10.1158\/0008-5472.CAN-07-1064","article-title":"Tumor necrosis factor-\u03b1 promotes malignant pleural effusion","volume":"67","author":"Stathopoulos","year":"2007","journal-title":"Cancer Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.tips.2016.04.006","article-title":"Exosome-mediated metastasis: from epithelial\u2013mesenchymal transition to escape from immunosurveillance","volume":"37","author":"Syn","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"B88","doi-asserted-by":"publisher","first-page":"20160479","DOI":"10.1098\/rstb.2016.0479","article-title":"Why the need and how to approach the functional diversity of extracellular vesicles","volume":"373","author":"Tkach","year":"2017","journal-title":"Philosophical Trans. R. Soc. B Biol. Sci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"151229","DOI":"10.1016\/j.ejcb.2022.151229","article-title":"Tetraspanins interweave EV secretion, endosomal network dynamics and cellular metabolism","volume":"101","author":"Toribio","year":"2022","journal-title":"Eur. J. Cell Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-1-0716-3203-1_11","article-title":"Two complementary strategies to quantitate extracellular vesicle uptake using bioluminescence and non-lipidic dyes","volume":"2668","author":"Toribio","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1111\/j.1398-9995.2012.02835.x","article-title":"Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma","volume":"67","author":"Torregrosa Paredes","year":"2012","journal-title":"Allergy"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide triggers budding of exosome vesicles into multivesicular endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"B93","doi-asserted-by":"publisher","first-page":"603","DOI":"10.5732\/cjc.011.10226","article-title":"Epithelial-mesenchymal transition in breast cancer progression and metastasis","volume":"30","author":"Wang","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"B94","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s001090050241","article-title":"Ligand-independent activation of steroid hormone receptors","volume":"76","author":"Weigel","year":"1998","journal-title":"J. Mol. Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e12182","DOI":"10.1002\/jev2.12182","article-title":"Updating MISEV: evolving the minimal requirements for studies of extracellular vesicles","volume":"10","author":"Witwer","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"B97","first-page":"4362","article-title":"Exosomes mediated transfer of lncRNA UCA1 results in increased tamoxifen resistance in breast cancer cells","volume":"20","author":"Xu","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1199631","DOI":"10.3389\/fimmu.2023.1199631","article-title":"Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy","volume":"14","author":"Xu","year":"2023","journal-title":"Front. Immunol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1083\/jcb.141.3.791","article-title":"Regulation of endothelial cell motility by complexes of tetraspan molecules CD81\/TAPA-1 and CD151\/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions","volume":"141","author":"Y\u00e1\u00f1ez-M\u00f3","year":"1998","journal-title":"J. Cell Biol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Y\u00e1\u00f1ez-M\u00f3","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"B101","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12943-023-01725-x","article-title":"Roles of tumor-associated macrophages in anti-PD-1\/PD-L1 immunotherapy for solid cancers","volume":"22","author":"Zhang","year":"2023","journal-title":"Mol. Cancer"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1158\/0008-5472.CAN-06-2295","article-title":"Colon cancer cell\u2013derived tumor necrosis factor-\u03b1 mediates the tumor growth\u2013promoting response in macrophages by up-regulating the colony-stimulating factor-1 pathway","volume":"67","author":"Zins","year":"2007","journal-title":"Cancer Res."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1548724\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:53:16Z","timestamp":1749714796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1548724\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":102,"alternative-id":["10.3389\/fcell.2025.1548724"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1548724","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]},"article-number":"1548724"}}