Distinct mesenchymal cell states mediate prostate cancer progression
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Published:2024-01-08
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Pakula Hubert, Omar MohamedORCID, Carelli Ryan, Pederzoli Filippo, Fanelli Giuseppe NicolòORCID, Pannellini Tania, Socciarelli Fabio, Van Emmenis LucieORCID, Rodrigues Silvia, Fidalgo-Ribeiro Caroline, Nuzzo Pier VitaleORCID, Brady Nicholas J.ORCID, Dinalankara Wikum, Jere MadhaviORCID, Valencia Itzel, Saladino Christopher, Stone Jason, Unkenholz Caitlin, Garner Richard, Alexanderani Mohammad K., Khani FrancescaORCID, de Almeida Francisca Nunes, Abate-Shen Cory, Greenblatt Matthew B.ORCID, Rickman David S.ORCID, Barbieri Christopher E.ORCID, Robinson Brian D.ORCID, Marchionni LuigiORCID, Loda MassimoORCID
Abstract
AbstractIn the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin’s role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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