{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:06Z","timestamp":1792788366741,"version":"4.5.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada","id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Triple-negative breast cancer is characterized by high rates of chemoresistance and poor clinical outcomes. Although ATP-binding cassette (ABC) transporters are well-established mediators of drug efflux, their role in tumor\u2013immune communication remains poorly defined. Here, we investigated whether the acquisition of doxorubicin resistance alters extracellular vesicle (EV) biogenesis and cargo content. We report that the doxorubicin-resistant MDA-MB-231 cell line exhibits significantly higher rates of EV production, without changes in particle size distribution, compared to the parental cell line. At the cellular level, we observed a significant increase in the number of multivesicular bodies present in doxorubicin-resistant cells. Proteomic and Western blot analysis of isolated EVs derived from the doxorubicin-resistant MDA-MB-231 cell line, compared to the parental MDA-MB-231 cell line, revealed an enrichment of ABCC1, accompanied by enrichment of vesicle-associated pathways. Cellular ABCC1 localized to CD63-positive compartments and was validated to be enriched in resistant cell line-derived EVs. Functionally, EVs from resistant cells promoted M2-like polarization of primary human macrophages, characterized by decreased CD86\u207a and increased CD206\u207a populations in addition to a decrease in IL-6, IL-8 and TNF\u03b1 levels. Knocking down ABCC1 in resistant cells significantly attenuated this effect. Together, these findings suggest EV-associated ABCC1 might be a contributor to macrophage polarization and immune modulation in breast cancer.<\/jats:p>","DOI":"10.1242\/jcs.265094","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:51:45Z","timestamp":1792666305000},"source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles from chemoresistant breast cancer cells reprogram macrophages toward an M2-like phenotype in an ABCC1-dependent manner"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4899-6578","authenticated-orcid":false,"given":"Sina","family":"Halvaei","sequence":"first","affiliation":[{"name":"1 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2059-8969","authenticated-orcid":false,"given":"Vignesh","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"1 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0373-5120","authenticated-orcid":false,"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"2 Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suganthi","family":"Chittaranjan","sequence":"additional","affiliation":[{"name":"3 Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Colborne","sequence":"additional","affiliation":[{"name":"2 Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Daly","sequence":"additional","affiliation":[{"name":"1 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8949-4374","authenticated-orcid":false,"given":"Gregg B.","family":"Morin","sequence":"additional","affiliation":[{"name":"3 Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC, Canada"},{"name":"4 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-4309","authenticated-orcid":false,"given":"Simon","family":"Wisnovsky","sequence":"additional","affiliation":[{"name":"1 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-8289","authenticated-orcid":false,"given":"Sharon M.","family":"Gorski","sequence":"additional","affiliation":[{"name":"3 Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC, Canada"},{"name":"5 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-2869","authenticated-orcid":false,"given":"Karla C.","family":"Williams","sequence":"additional","affiliation":[{"name":"1 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.265094\/3722401\/jcs265094.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.265094\/3722401\/jcs265094.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:51:46Z","timestamp":1792666306000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.265094\/373236\/Extracellular-vesicles-from-chemoresistant-breast"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/jcs.265094","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"article-number":"jcs.265094"}}