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

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

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.

MeSH terms

  • Animals
  • Breast Neoplasms / physiopathology*
  • Cell Separation
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophages / cytology*
  • Mammary Neoplasms, Animal / physiopathology*
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Phenotype
  • Receptor, ErbB-2 / metabolism
  • Transcriptome
  • Tumor Microenvironment / genetics

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2

Grant support

David Vallerand was paid by ROCHE laboratories and a part of experiments was supported by ROCHE laboratories (CIFRE PhD grant 2010/0553). Stefan Weigand and Ariel Savina were employed by Roche Diagnostics GmbH. Pierre De La Grange was employed by GenoSplice Technology. The specific roles of these authors are articulated in the “author contributions” section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.