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Aberrant vascularization is a hallmark of cancer, although the contribution of pericytes to this process is poorly understood. Here, we undertook a combined computational and experimental approach to identify the molecular reprogramming of prostate pericytes during cancer pathogenesis and progression. Analysis of human prostate cancer and murine models showed that prostate tumors exhibit a disequilibrium between endothelial and pericyte content with prognostic potential. Deeper molecular analysis revealed that there is no overt loss of pericytes in prostate tumors but rather a dysfunction that is concomitant with altered expression of a subset of cellular markers. We translate this finding into a simplified signature that discriminates pericyte abundance versus function. Leveraging single\u2010cell RNA sequencing data, we find that TGF\u2010\u03b2 governs the molecular changes that underlie pericyte dysfunction in tumors. This mechanism is associated with reduced expression of contractility markers, enlargement of the vascular lumen, and increased permeability in prostate cancer. This study revisits the paradigm of the reduced number of pericytes in favor of their dysfunction in tumors and the importance of paracrine signaling in this process.<\/jats:p>","DOI":"10.1002\/1878-0261.70135","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:16:29Z","timestamp":1761070589000},"page":"947-961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aggressive prostate cancer is associated with pericyte dysfunction"],"prefix":"10.1002","volume":"20","author":[{"given":"Anabel","family":"Martinez\u2010Romero","sequence":"first","affiliation":[{"name":"Endothelial Pathobiology and Microenvironment Group Josep Carreras Leukaemia Research Institute (IJC)  Barcelona Catalonia Spain"},{"name":"Department of Physiological Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane","family":"Martinez\u2010Larrinaga","sequence":"additional","affiliation":[{"name":"Endothelial Pathobiology and Microenvironment Group Josep Carreras Leukaemia Research Institute (IJC)  Barcelona Catalonia Spain"},{"name":"Department of Physiological Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)  Derio Spain"},{"name":"CIBERONC, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Grego\u2010Bessa","sequence":"additional","affiliation":[{"name":"Endothelial Pathobiology and Microenvironment Group Josep Carreras Leukaemia Research Institute (IJC)  Barcelona Catalonia Spain"},{"name":"Advanced Microscopy Unit. 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