{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T10:05:05Z","timestamp":1763460305508,"version":"3.45.0"},"reference-count":63,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas CONAHCYT, Mexico","doi-asserted-by":"publisher","award":["CBF-2025-I-4446"],"award-info":[{"award-number":["CBF-2025-I-4446"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONAHCYT doctoral scholarship","award":["727202"],"award-info":[{"award-number":["727202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, driven by late diagnosis, limited therapeutic options, and high metastatic potential. Beyond their canonical roles in hemostasis, platelets have emerged as active modulators of tumor progression and promising noninvasive biomarkers. Among platelet-associated molecules, \u03b1-defensins, particularly Defensin Alpha 1\/3 (DEFA1\/3), have been implicated in inflammation and immunity; however, their contribution to PDAC pathogenesis remains unclear. We combined bioinformatic analysis of platelet transcriptomes with functional and in vivo zebrafish xenograft validation to investigate the impact of DEFA1\/3 on PDAC aggressiveness. DEFA1\/3 was significantly upregulated in PDAC-derived platelets. Defensin-enriched platelet-like particles (defensin-rich platelets, DRPs) and recombinant DEFA1\/3 enhanced pancreatic cancer cell proliferation, migration, and three-dimensional growth in vitro and promoted tumor dissemination in zebrafish xenografts. Transcriptomic profiling revealed the upregulation of SPARC, KDM6A, and GATA6, whereas clinical data from The Cancer Genome Atlas (TCGA)-PDAC linked high DEFA1\/3 expression to poor survival, increased immune infiltration, and activation of epithelial\u2013mesenchymal transition (EMT). Platelet-derived DEFA1\/3 acts as a functional modulator of PDAC progression, linking platelet granule content to tumor aggressiveness and highlighting a potential biomarker and therapeutic target within the platelet\u2013tumor axis.<\/jats:p>","DOI":"10.3390\/ijms262210898","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:08Z","timestamp":1762782668000},"page":"10898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defensin-Rich Platelets Drive Pro-Tumorigenic Programs in Pancreatic Adenocarcinoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-4061","authenticated-orcid":false,"given":"Jonathan","family":"Gonzalez-Ruiz","sequence":"first","affiliation":[{"name":"Department of Ciencias de la Salud, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09310, Mexico"},{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2800-5540","authenticated-orcid":false,"given":"Miryam","family":"Sarmiento-Casas","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-3573","authenticated-orcid":false,"given":"Ivan","family":"Bahena-Ocampo","sequence":"additional","affiliation":[{"name":"Department of Ciencias de la Salud, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09310, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4657-6382","authenticated-orcid":false,"given":"Magali","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4880-7084","authenticated-orcid":false,"given":"Gisela","family":"Ceballos-Cancino","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-2494","authenticated-orcid":false,"given":"Karla","family":"Vazquez-Santillan","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-5961","authenticated-orcid":false,"given":"Vilma","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Laboratorio de Epigen\u00e9tica, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-1607","authenticated-orcid":false,"given":"Jorge","family":"Melendez-Zajgla","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Funcional del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Antunes-Ferreira, M., D\u2019Ambrosi, S., Arkani, M., Post, E., In\u2019t Veld, S.G.J.G., Ramaker, J., Zwaan, K., Kucukguzel, E.D., Wedekind, L.E., and Griffioen, A.W. 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