{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T21:34:00Z","timestamp":1762896840658,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Libyan Ministry of Higher Education"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>Several of the integrin family of cell adhesion receptors have been popular targets for the development of anticancer agents, but with little clinical success to date. Cancer cells usually express multiple redundant integrins; one hypothesis for the lack of efficacy of current antagonists is their high selectivity for a single integrin. To address this, we developed a functional dual-\u03b23-expressing cell model to investigate the effects of combined \u03b1IIb\u03b23\/\u03b1v\u03b23 antagonism. We established that treating K562 chronic myeloid leukemia cells with 0.04 \u03bcM phorbol 12-myristate 13-acetate (PMA) for 40 h significantly upregulates functional \u03b1IIb\u03b23 and \u03b1v\u03b23 integrins. This optimized method provides a reliable platform for adhesion and detachment assays, enabling the characterization of dual integrin targeting strategies. Using this model, we demonstrate that combining \u03b1IIb\u03b23 and \u03b1v\u03b23 antagonists (GR144053 and cRGDfV) synergistically enhances inhibition of cell adhesion and promotes cell detachment compared to single-agent treatments. Our findings establish a reproducible approach for studying dual \u03b23 integrin targeting, which can be used to investigate potential strategies for overcoming integrin redundancy in cancer therapeutics.<\/jats:p>","DOI":"10.3390\/mps8040073","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T10:03:27Z","timestamp":1751882607000},"page":"73","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["K562 Chronic Myeloid Leukemia Cells as a Dual \u03b23-Expressing Functional Cell Line Model to Investigate the Effects of Combined \u03b1IIb\u03b23 and \u03b1v\u03b23 Antagonism"],"prefix":"10.3390","volume":"8","author":[{"given":"Amal A.","family":"Elsharif","sequence":"first","affiliation":[{"name":"Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence H.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4647-2340","authenticated-orcid":false,"given":"Steven D.","family":"Shnyder","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-2132","authenticated-orcid":false,"given":"Helen M.","family":"Sheldrake","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.131.3.791","article-title":"Integrin function: Molecular hierarchies of cytoskeletal and signaling molecules","volume":"131","author":"Miyamoto","year":"1995","journal-title":"J. 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