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PLoS One. 2016 Jul 7;11(7):e0157670. doi: 10.1371/journal.pone.0157670. eCollection 2016.

Characterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization.

Author information

1
Translational Research Department, Laboratory of Preclinical Investigation, Institut Curie, PSL University, Paris, France.
2
Institut Roche, Boulogne-Billancourt, France.
3
Department of Pathology, Institut Curie, Paris, France.
4
Platform of Molecular Biology Facilities, Institut Curie, PSL University, Paris, France.
5
Flow Cytometry Core Facility, Institut Curie, PSL University, Paris, France.
6
GenoSplice Technology, Institut Universitaire d'Hématologie, Paris, France.
7
Inserm, U830, Institut Curie, PSL University, Paris, France.
8
CNRS UMR3306, INSERM U1005, Institut Curie, PSL University, Orsay, France.
9
Department of Medical Oncology, Institut Curie, Institut Curie, Paris, France.
10
Roche Diagnostics GmbH, Penzberg, Germany.
11
Translational Research Department, Institut Curie, PSL University, Paris, France.

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.

PMID:
27388901
PMCID:
PMC4936680
DOI:
10.1371/journal.pone.0157670
[Indexed for MEDLINE]
Free PMC Article

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