{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T18:14:22Z","timestamp":1769710462096,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471362"],"award-info":[{"award-number":["32471362"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2025A04J4701"],"award-info":[{"award-number":["2025A04J4701"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012606"],"award-info":[{"award-number":["2023A1515012606"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Circulating tumor cells (CTCs) utilize platelets to withstand hemodynamic stress and evade immune clearance; however, the mechanisms driving platelet\u2013cancer cell aggregation under flow remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigated which physical quantity\u2014shear rate, exposure time, or an integrated metric\u2014governs the aggregation and identified the key adhesion molecules involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human platelets and EGFR\u2010mutant lung adenocarcinoma PC\u20109 cells were fluorescently labeled, mixed at a 10:1 ratio, and subjected to mechanical stimulation using a vortex mixer or a TA ARES G2 rheometer across shear rates 0\u20134050\u2009s\n                      <jats:sup>\u22121<\/jats:sup>\n                      and durations of 0\u20134860\u2009s. Aggregates were quantified by flow cytometry via dual\u2010positive gating. The functional roles of platelet P\u2010selectin and CD40 ligand (CD40L) were assessed using antibodies Inclacumab and 5c8, respectively. Shear significantly promoted platelet\u2013PC\u20109 aggregation compared with static conditions, while blocking P\u2010selectin or CD40L markedly suppressed this effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Aggregation exhibited a biphasic dependence on both shear rate and exposure time. Notably, when plotting aggregation against shear accumulation (rate \u00d7 time), all data converged onto a unified biphasic curve with an optimum of ~27\u2009000.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate that platelet\u2013PC\u20109 aggregation is governed by a shear accumulation\u2013dependent mechanism, optimized under moderate shear and finite exposure, and regulated by P\u2010selectin and CD40L. These findings provide new biophysical insights into transient platelet\u2010PC\u20109 interactions in circulation and suggest that targeting platelet activation pathways or modulating hemodynamics may prevent hematogenous metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.70047","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:40:13Z","timestamp":1767199213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aggregation of Platelets and Human\n                    <scp>EGFR<\/scp>\n                    Mutant Lung Adenocarcinoma Cells Under Flow Is Governed by Shear Accumulation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3438-1425","authenticated-orcid":false,"given":"Xiaoxi","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medical Research, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-3268","authenticated-orcid":false,"given":"Jiangguo","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3004"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04131.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2018.01.035"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25122835"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1023865"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025320"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.12.3740"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-145821"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.3.880"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.225169"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2012.760"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11433-013-5270-7"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.04.018"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310294"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2021.12.027"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10334-6"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0669-2"},{"issue":"5","key":"e_1_2_12_20_1","first-page":"450","article-title":"Interaction Between Circulating Cancer Cells and Platelets: Clinical Implication","volume":"27","author":"Lou X. 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