Year: 2015
Type: article
Abstract: 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.
Source: Nature Communications
DOI: 10.1038/ncomms9695
Authors: 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
Institutions: University of Salerno, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Azienda Ospedaliero-Universitaria Careggi, Centre National de la Recherche Scientifique, Institut de Génétique Moléculaire de Montpellier, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, University of Chieti-Pescara, Ospedale SS. Annunziata, University of California San Diego, University of Utah, Huntsman Cancer Institute, Cold Spring Harbor Laboratory
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1529346103, G995807686
OpenAlex ID: W2200997261