{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:43:13Z","timestamp":1777495393267,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Veterans Affairs","award":["1OBX000705"],"award-info":[{"award-number":["1OBX000705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to reproduce a more physiological environment that NK3.3EVs would encounter in vivo. NK3.3EVs penetrated MCF7 mammospheres, inducing death by apoptosis. We generated an imatinib-resistant K562 chronic myeloid leukemia (CML) cell line to investigate whether NK3.3EVs were able to kill tumor cells resistant to front-line chemotherapy. NK3.3EVs were even more cytotoxic to imatinib-resistant cells than parental cells, inducing apoptosis via caspase-3\/-7 activation. The small population of cancer stem cells (CSCs) within tumors also contributes to therapeutic resistance. NK3.3EVs reduced the CSC-like CD34+\/CD38\u2212 subpopulation in imatinib-resistant and parental K562 cultures and decreased CSC-associated expression of tumor-promoting genes. Our results provide strong evidence that NK3.3EVs may be a potential new immunotherapeutic agent for difficult-to-treat cancers.<\/jats:p>","DOI":"10.3390\/cancers16010090","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:49:27Z","timestamp":1703450967000},"page":"90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Allyson","family":"McCune","sequence":"first","affiliation":[{"name":"Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacki","family":"Kornbluth","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"},{"name":"St. Louis VA Medical Center, St. Louis, MO 63106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.stem.2018.12.009","article-title":"Cancer Stem Cells: The Architects of the Tumor Ecosystem","volume":"24","author":"Prager","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1001\/jamaoncol.2021.6987","article-title":"Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"8","author":"Kocarnik","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.biotechadv.2016.11.002","article-title":"3D tumor spheroids: An overview of the tools and techniques used for their analysis","volume":"34","author":"Costa","year":"2016","journal-title":"Biotechnol. 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