{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:01:45Z","timestamp":1784818905583,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012819","name":"Egyptian Cultural and Educational Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cancer\u2010associated fibroblasts (CAFs) are key cell types within the tumor microenvironment (TME), responsible for their pro\u2010tumorigenic effects and metastasis. Specifically, inflammatory CAFs (iCAFs), a CAF subtype, are known to induce tumor cell progression, migration, and immunosuppression. Fibroblast growth factor receptors (FGFRs) play a crucial role in cell differentiation, migration, and proliferation. In this study, we investigated the effect of FGFR kinase inhibitor AZD4547 (AZD), a clinical\u2010stage drug, on iCAF differentiation and iCAF\u2010mediated effects on the tumor\u2010stroma interaction in\u00a0vitro and in\u00a0vivo. Treatment with AZD inhibited the differentiation of human pancreatic stellate cells into iCAFs using IL\u20101\u03b1, as shown with reduced IL\u20106 expression. FGFR1, 2, 3, and 4 were upregulated in iCAFs, which were inhibited by AZD. Treatment with AZD also attenuated the iCAF\u2010mediated paracrine effect on the PDAC cell\u2010induced migration and epithelial\u2010mesenchymal transition of tumor cells, as well as polarization of macrophages towards the M1 phenotype in\u00a0vitro. Furthermore, AZD significantly reduced the growth of tumor cells and fibroblasts in co\u2010cultured 3D heterospheroids in\u00a0vitro. In\u00a0vivo, treatment with AZD attenuated the tumor growth in the syngeneic subcutaneous KPC murine tumor model. Interestingly, flow cytometry and immunofluorescent staining analyses on isolated tumors revealed that AZD\u2010treated tumors had a reduced iCAF population and M2\u2010type macrophages. Furthermore, we found that AZD treatment reduced the liver metastasis, as shown with the reduction of ki\u201067 and p53 tumor markers in the AZD\u2010treated group compared to the vehicle group. Altogether, this study demonstrates that FGFRs are overexpressed on iCAFs and their inhibition using AZD diminishes iCAF\u2010mediated paracrine signaling with tumor cells and macrophages, thereby attenuating tumor growth and metastasis.<\/jats:p>","DOI":"10.1096\/fj.202504573rr","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:51:23Z","timestamp":1783061483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>FGFR<\/scp>\n                    Inhibitor\n                    <scp>AZD4547<\/scp>\n                    Disrupts Inflammatory\n                    <scp>CAF<\/scp>\n                    Crosstalk With Cancer Cells and Macrophages and Attenuates Metastasis in Pancreatic Cancer"],"prefix":"10.1096","volume":"40","author":[{"given":"Ahmed M. R. 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