A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth

By Binzhi Qian, Yan Deng, J. Im, Ruth J. Muschel, Y. Zou, Jiu-feng Li, R. Lang, J. Pollard. PLoS ONE, 2009

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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.

Subfields: Biotechnology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/6f85c4d85b0a1af4dd62577320f7d00217ee6a33

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Citations in the corpus

Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications (2019, background): “The intimate contacts between tumor cells and macrophages during extravasation were visualized and quantitatively analyzed within an intact lung imaging system [115].”
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Macrophages and therapeutic resistance in cancer (2015, positive): “neoplastic cells in response to molecules secreted by macrophages (DeNardo et al., 2009; Mizutani et al., 2009; Qian et al., 2009).”
Tumor-associated macrophages: from mechanisms to therapy (2014, background): “Monocytes and/or macrophages are essential metastasis promoters acting both to prepare sites and also to promote the extravasation, survival, and persistent growth of metastatic cells (Joyce and Pollard, 2009; Qian et al., 2009).”
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