Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
16 Sep 2024
Historique:
received: 06 12 2023
revised: 13 06 2024
accepted: 22 08 2024
medline: 21 9 2024
pubmed: 21 9 2024
entrez: 20 9 2024
Statut: aheadofprint

Résumé

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10

Identifiants

DOI: 10.1016/j.ccell.2024.08.018 PMID: 39303726
pubmed: 39303726
pii: S1535-6108(24)00317-9
doi: 10.1016/j.ccell.2024.08.018
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Authors declare no competing interests.

Auteurs

Bianca Calì (B)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Martina Troiani (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Silvia Bressan (S)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy.

Giuseppe Attanasio (G)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Sara Merler (S)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Section of Oncology, Department of Medicine, University of Verona, 37134 Verona, Italy; Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, CH6500 Bellinzona, Switzerland; Veneto Institute of Molecular Medicine, 35129 Padova, Italy.

Viola Moscarda (V)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Section of Oncology, Department of Medicine, University of Verona, 37134 Verona, Italy.

Simone Mosole (S)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Elena Ricci (E)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.

Christina Guo (C)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Wei Yuan (W)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Lewis Gallagher (L)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Arian Lundberg (A)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Ilona Bernett (I)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Ines Figueiredo (I)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Rydell Alvarez Arzola (RA)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Department of Immunoregulation, Immunology and Immunotherapy Division, Center of Molecular Immunology, La Habana 3GGH+C9G, Cuba.

Ernesto Bermudez Abreut (EB)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Department of Immunoregulation, Immunology and Immunotherapy Division, Center of Molecular Immunology, La Habana 3GGH+C9G, Cuba.

Mariantonietta D'Ambrosio (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Nicolò Bancaro (N)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Daniela Brina (D)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Sara Zumerle (S)

Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Department of Medicine, University of Padova, 35121 Padova, Italy.

Emiliano Pasquini (E)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Martino Maddalena (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Ping Lai (P)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Manuel Colucci (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Nicolò Pernigoni (N)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Andrea Rinaldi (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Davide Minardi (D)

Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Urology Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.

Alessandro Morlacco (A)

Urology Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.

Fabrizio Dal Moro (FD)

Urology Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.

Marianna Sabbadin (M)

Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Department of Medicine, Surgical Pathology Unit, University of Padova, 35121 Padova, Italy.

Francesca Galuppini (F)

Department of Medicine, Surgical Pathology Unit, University of Padova, 35121 Padova, Italy.

Matteo Fassan (M)

Department of Medicine, Surgical Pathology Unit, University of Padova, 35121 Padova, Italy.

Jan Hendrik Rüschoff (JH)

Department of Pathology and Molecular Pathology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.

Holger Moch (H)

Department of Pathology and Molecular Pathology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.

Pasquale Rescigno (P)

Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Turin, Italy.

Edoardo Francini (E)

Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, CH6500 Bellinzona, Switzerland; Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.

Calogero Saieva (C)

Cancer Risk Factors and Lifestyle Epidemiology Unit - ISPRO, 50139 Florence, Italy.

Mikol Modesti (M)

Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, CH6500 Bellinzona, Switzerland.

Jean-Philippe Theurillat (JP)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.

Silke Gillessen (S)

Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, CH6500 Bellinzona, Switzerland.

Petra Wilgenbus (P)

Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany; Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA.

Claudine Graf (C)

Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany; Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA.

Wolfram Ruf (W)

Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany; Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA.

Johann de Bono (J)

The Institute of Cancer Research, The Royal Marsden Hospital, London SW3 6JJ, UK.

Andrea Alimonti (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland; Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, CH6500 Bellinzona, Switzerland; Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Department of Medicine, University of Padova, 35121 Padova, Italy; Department of Health Sciences and Technology (D-HEST) ETH Zurich, 8092 Zurich, Switzerland. Electronic address: andrea.alimonti@ior.usi.ch.

Classifications MeSH