A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth
Bin-Zhi Qian,Yan Deng,Jae Hong Im,Ruth J. Muschel,Yiyu Zou,Jiufeng Li,Richard A. Lang,Jeffrey W. Pollard +7 more
TLDR
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 metastasis.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.read more
Citations
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Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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Macrophage Diversity Enhances Tumor Progression and Metastasis
Bin-Zhi Qian,Jeffrey W. Pollard +1 more
TL;DR: There is persuasive clinical and experimental evidence that macrophages promote cancer initiation and malignant progression, and specialized subpopulations of macrophage may represent important new therapeutic targets.
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Coordinated regulation of myeloid cells by tumours
TL;DR: This work considers myeloid cells as an intricately connected, complex, single system and focuses on how tumours manipulate the myeloids system to evade the host immune response.
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Tumor-associated macrophages: from mechanisms to therapy.
TL;DR: Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.
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CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
Bin-Zhi Qian,Jiufeng Li,Hui Zhang,Takanori Kitamura,Jinghang Zhang,Liam Campion,Elizabeth Kaiser,Linda A. Snyder,Jeffrey W. Pollard +8 more
TL;DR: The mechanistic link between CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer and the origin of these macrophages is defined by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice.
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