{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:54:44Z","timestamp":1791543284478,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"56","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Abnormal tumor vasculature creates a permissive microenvironment that fuels the malignant progression of bladder cancer (BCa). While Leucine\u2010rich alpha\u20102 glycoprotein 1 (LRG1) is known to regulate angiogenesis, its specific role in remodeling the BCa microenvironment remains poorly defined.We integrated single\u2010cell RNA sequencing (scRNA\u2010seq) with bulk transcriptomic datasets to identify key cellular subclusters. Functional validation was performed using subcutaneous and orthotopic BCa mouse models, neutrophil depletion, DNase I treatment, and clinical specimens. The molecular interactome was mapped via pull\u2010down assays, mass spectrometry, and confocal imaging.LRG1 is significantly upregulated in BCa and correlates with hematogenous metastasis and poor prognosis. Mechanistically, tumor\u2010derived LRG1 binds to Annexin A2 (ANXA2) on neutrophils through its LRR domain, impeding the mitochondrial translocation of Akt and triggering mtROS\u2010dependent release of Neutrophil Extracellular Traps (NETs). These NETs directly cause vascular destabilization by stripping mural cell coverage. Blockade of the LRG1\u2010NETosis axis induces vascular normalization, effectively overcoming microenvironmental barriers to increase drug delivery and T\u2010cell infiltration, thereby profoundly sensitizing BCa to cisplatin and anti\u2010PD\u20101 therapy.The LRG1\u2010neutrophil\u2010NETosis axis is a critical driver of vascular dysfunction and therapeutic resistance in BCa. Targeting this axis represents a promising translational strategy to improve clinical outcomes.<\/jats:p>","DOI":"10.1002\/advs.76604","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:12:52Z","timestamp":1783944772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LRG1 Drives Pathological Angiogenesis by Disrupting Neutrophil Mitochondrial Homeostasis in Bladder Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3479-3144","authenticated-orcid":false,"given":"Dongshan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Qilu Hospital of Shandong University  Jinan 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