Aggressive prostate cancer is associated with pericyte dysfunction
Pericytes are intrinsic components of vessels that regulate vascular stability and permeability. 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-cell RNA sequencing data, we find that TGF-β 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.
Authors
- Arkaitz Carracedo (ORCID: https://orcid.org/0000-0001-5957-1260)
- Joaquím Grego‐Bessa (ORCID: https://orcid.org/0000-0002-0938-2346)
- Amaia Ercilla (ORCID: https://orcid.org/0000-0001-8999-7131)
- Mariona Graupera (ORCID: https://orcid.org/0000-0003-4608-4185)
- Laura Bozal‐Basterra (ORCID: https://orcid.org/0000-0002-4858-2199)
- Isabel Mendizabal (ORCID: https://orcid.org/0000-0002-9018-3474)
- Anabel Martínez-Romero (ORCID: https://orcid.org/0000-0001-5626-6674)
- Pilar Villacampa (ORCID: https://orcid.org/0000-0002-2860-7475)
- Ianire Astobiza (ORCID: https://orcid.org/0000-0002-7142-7066)
- Hielke van Splunder
- Saioa Garcia‐Longarte (ORCID: https://orcid.org/0000-0001-5412-4234)
- Ane Martinez‐Larrinaga (ORCID: https://orcid.org/0000-0001-9791-915X)
Institutions
- Ikerbasque (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of the Basque Country (ES)
- Instituto de Salud Carlos III (ES)
- BioCruces Health research Institute (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- CIC bioGUNE (ES)
- Department of Physiological Sciences (RU)
- Fundación Josep Carreras Contra la Leucemia (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Molecular Oncology
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1002/1878-0261.70135
- Primary Topic
- Angiogenesis and VEGF in Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación BBVA
- “la Caixa” Foundation
- Department of Industry, Tourism and Trade
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Banco Bilbao Vizcaya Argentaria
- Horizon 2020 Framework Programme
- Agencia Estatal de Investigación