A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth

Binzhi Qian, Yan Deng, Jae Hong Im, Ruth J. Muschel, Yiyu Zou, Jiufeng Li, Richard A. Lang, Jeffrey W. Pollard

Research output: Contribution to journalArticle

376 Scopus citations

Abstract

Background: The stromal microenvironment and particularly the macrophage component of primary tumors influence their malignant potential. However, at the metastatic site the role of these cells and their mechanism of actions for establishment and growth of metastases remain largely unknown. Methodology/Principal Findings: Using animal models of breast cancer metastasis, we show that a population of host macrophages displaying a distinct phenotype is recruited to extravasating pulmonary metastatic cells regardless of species of origin. Ablation of this macrophage population through three independent means (genetic and chemical) showed that these macrophages are required for efficient metastatic seeding and growth. Importantly, even after metastatic growth is established, ablation of this macrophage population inhibited subsequent growth. Furthermore, imaging of intact lungs revealed that macrophages are required for efficient tumor cell extravasation. Conclusion/Significance: These data indicate a direct enhancement of metastatic growth by macrophages through their effects on tumor cell extravasation, survival and subsequent growth and identifies these cells as a new therapeutic target for treatment of metastatic disease.

Original languageEnglish (US)
Article numbere6562
JournalPloS one
Volume4
Issue number8
DOIs
StatePublished - Aug 10 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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