title: Characterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization.
abstract: Drug discovery efforts have focused on the tumor microenvironment in recent years. However, few studies have characterized the stroma component in patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMs). In this study, we characterized the stroma in various models of breast cancer tumors in mice. We performed transcriptomic and flow cytometry analyses on murine populations for a series of 25 PDXs and the two most commonly used GEMs (MMTV-PyMT and MMTV-erBb2). We sorted macrophages from five models. We then profiled gene expression in these cells, which were also subjected to flow cytometry for phenotypic characterization. Hematopoietic cell composition, mostly macrophages and granulocytes, differed between tumors. Macrophages had a specific polarization phenotype related to their M1/M2 classification and associated with the expression of genes involved in the recruitment, invasion and metastasis processes. The heterogeneity of the stroma component of the models studied suggests that tumor cells modify their microenvironment to satisfy their needs. Our observations suggest that such models are of relevance for preclinical studies.
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.|Institut Roche, Boulogne-Billancourt, France.
authors.forename: David
authors.initials: D
authors.lastname: Vallerand
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Massonnet
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Kébir
authors.affiliation: Platform of Molecular Biology Facilities, Institut Curie, PSL University, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.affiliation: Flow Cytometry Core Facility, Institut Curie, PSL University, Paris, France.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Maciorowski
authors.affiliation: GenoSplice Technology, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: De la Grange
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.|Inserm, U830, Institut Curie, PSL University, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Richardson
authors.affiliation: CNRS UMR3306, INSERM U1005, Institut Curie, PSL University, Orsay, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humbert
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Thuleau
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Assayag
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
authors.forename: Ludmilla
authors.initials: L
authors.lastname: de Plater
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Department of Medical Oncology, Institut Curie, Institut Curie, Paris, France.
authors.forename: Suzy
authors.initials: S
authors.lastname: Scholl
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weigand
authors.affiliation: Translational Research Department, Institut Curie, PSL University, Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Institut Roche, Boulogne-Billancourt, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
authors.affiliation: Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.|Department of Medical Oncology, Institut Curie, Institut Curie, Paris, France.|Translational Research Department, Institut Curie, PSL University, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D015674:Mammary Neoplasms, Animal / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human