BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

Alessandra Rosati; Anna Basile; Raffaella D’Auria; Morena d’Avenia; Margot De Marco; Antonia Falco; Michelina Festa; Luana Guerriero; Vittoria Iorio; Roberto Parente; Maria Pascale; Liberato Marzullo; Renato Franco; Claudio Arra; Antonio Barbieri; Domenica Rea; Giulio Menichini; Michael Hahne; Maarten Bijlsma; Daniela Barcaroli; Gianluca Sala; Fabio Francesco di Mola; Pierluigi di Sebastiano; Jelena Todoric; Laura Antonucci; Vincent Corvest; Anass Jawhari; Matthew A Firpo; David A Tuveson; Mario Capunzo; Michael Karin; Vincenzo De Laurenzi; Maria Caterina Turco

doi:10.1038/ncomms9695

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BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

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BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

Alessandra Rosati, Anna Basile, Raffaella D’Auria, Morena d’Avenia, Margot De Marco, Antonia Falco, Michelina Festa, Luana Guerriero, Vittoria Iorio, Roberto Parente, …

Nature communications, Vol.6(1), pp.8695-8695

02/11/2015

DOI: https://doi.org/10.1038/ncomms9695

PMID: 26522614

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Article

Humanities and Social Sciences

multidisciplinary

Science

Science (multidisciplinary)

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential. BAG3 is found in the serum of pancreatic cancer patients and can be used as a marker of disease, but its role in cancer is unclear. Here, the authors show that BAG3 secreted from tumour cells binds to and activates macrophages, which in turn promotes cell growth, and an antibody blocking BAG3 binding reduces tumour formation in mice.

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Titre: BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages
Créateurs - sans rôle: Alessandra Rosati - BIOUNIVERSA s.r.l., Department of Medicine and Surgery, University of Salerno
Anna Basile - BIOUNIVERSA s.r.l., Department of Medicine and Surgery, University of Salerno
Raffaella D’Auria - BIOUNIVERSA s.r.l., Department of Pharmacy, Division of Biomedicine “A. Leone”, University of Salerno
Morena d’Avenia - BIOUNIVERSA s.r.l
Margot De Marco - BIOUNIVERSA s.r.l
Antonia Falco - BIOUNIVERSA s.r.l., Department of Pharmacy, Division of Biomedicine “A. Leone”, University of Salerno
Michelina Festa - BIOUNIVERSA s.r.l., Department of Pharmacy, Division of Biomedicine “A. Leone”, University of Salerno
Luana Guerriero - BIOUNIVERSA s.r.l., Department of Pharmacy, Division of Biomedicine “A. Leone”, University of Salerno
Vittoria Iorio - BIOUNIVERSA s.r.l., Department of Medicine and Surgery, University of Salerno
Roberto Parente - BIOUNIVERSA s.r.l
Maria Pascale - BIOUNIVERSA s.r.l., Department of Pharmacy, Division of Biomedicine “A. Leone”, University of Salerno
Liberato Marzullo - BIOUNIVERSA s.r.l., Department of Medicine and Surgery, University of Salerno
Renato Franco - Pathology Unit, Istituto Nazionale Tumouri Fondazione “G. Pascale”
Claudio Arra - Animal facility, Istituto Nazionale Tumouri Fondazione “G. Pascale”
Antonio Barbieri - Animal facility, Istituto Nazionale Tumouri Fondazione “G. Pascale”
Domenica Rea - Animal facility, Istituto Nazionale Tumouri Fondazione “G. Pascale”
Giulio Menichini - Department of Oncology, Reconstructive Microsurgery, Careggi University Hospital
Michael Hahne - Institut de Génétique Moléculaire de Montpellier
Maarten Bijlsma - Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam
Daniela Barcaroli - Dipartimento di Scienze Mediche, Orali e Biotecnologiche, University “G. d’Annunzio” di Chieti-Pescara, Centro Studi sull’Invecchiamento, CeSI-MeT
Gianluca Sala - Dipartimento di Scienze Mediche, Orali e Biotecnologiche, University “G. d’Annunzio” di Chieti-Pescara, Centro Studi sull’Invecchiamento, CeSI-MeT
Fabio Francesco di Mola - Division of Surgical Oncology, “S.S. Annunziata”Hospital
Pierluigi di Sebastiano - Division of Surgical Oncology, “S.S. Annunziata”Hospital
Jelena Todoric - Laboratory of Gene Regulation and Signal Transduction Departments of Pharmacology and Pathology, Laboratory of Gene Regulation and Signal Transduction, UCSD, School of Medicine
Laura Antonucci - Laboratory of Gene Regulation and Signal Transduction Departments of Pharmacology and Pathology, Laboratory of Gene Regulation and Signal Transduction, UCSD, School of Medicine
Vincent Corvest - CALIXAR, Bioparc, Bâtiment Laënnec
Anass Jawhari - CALIXAR, Bioparc, Bâtiment Laënnec
Matthew A Firpo - Department of Surgery, Huntsman Cancer Institute, University of Utah School of Medicine
David A Tuveson - Cold Spring Harbor Laboratory
Mario Capunzo - Department of Medicine and Surgery, University of Salerno
Michael Karin - Laboratory of Gene Regulation and Signal Transduction Departments of Pharmacology and Pathology, Laboratory of Gene Regulation and Signal Transduction, UCSD, School of Medicine
Vincenzo De Laurenzi - CESI
Maria Caterina Turco - University of Salerno
Détails de publication: Nature communications, Vol.6(1), pp.8695-8695
Éditeur: Nature Publishing Group UK
Identifiants: 99153915709311
Unité académique: Institut de Génétique Moléculaire de Montpellier - IGMM
Langue: English
Type de ressource: Journal article