Open AccessCharacterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization
Author(s) -
David Vallerand,
Gérald Massonnet,
F. Z. El Kébir,
David Gentien,
Zofia Maciorowski,
Pierre de la Grange,
Brigitte SigalZafrani,
Matthew Richardson,
Sandrine Humbert,
Aurélie Thuleau,
Franck Assayag,
Ludmilla de Plater,
Nicolas André,
Suzy Scholl,
Elisabetta Marangoni,
Stefan Weigand,
Sergio Roman-Roman,
Ariel Savina,
Didier Decaudin
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0157670
Subject(s) - biology , tumor microenvironment , stroma , flow cytometry , cancer research , metastasis , phenotype , macrophage polarization , transcriptome , mass cytometry , haematopoiesis , immunophenotyping , cancer , pathology , immunology , microbiology and biotechnology , gene expression , stem cell , gene , medicine , genetics , tumor cells , immunohistochemistry
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.