CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Bin Zhi Qian, Jiufeng Li, Hui Zhang, Takanori Kitamura, Jinghang Zhang, Liam R. Campion, Elizabeth A. Kaiser, Linda A. Snyder, Jeffrey W. Pollard

Research output: Contribution to journalArticle

1091 Citations (Scopus)

Abstract

Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)222-225
Number of pages4
JournalNature
Volume475
Issue number7355
DOIs
StatePublished - Jul 14 2011

Fingerprint

Monocytes
Breast Neoplasms
Neoplasm Metastasis
Macrophages
Neoplasms
CCR2 Receptors
Lung
Tumor Microenvironment
Chemokine CCL2
Vascular Endothelial Growth Factor A
Growth
Population

ASJC Scopus subject areas

  • General

Cite this

Qian, B. Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., ... Pollard, J. W. (2011). CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature, 475(7355), 222-225. https://doi.org/10.1038/nature10138

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. / Qian, Bin Zhi; Li, Jiufeng; Zhang, Hui; Kitamura, Takanori; Zhang, Jinghang; Campion, Liam R.; Kaiser, Elizabeth A.; Snyder, Linda A.; Pollard, Jeffrey W.

In: Nature, Vol. 475, No. 7355, 14.07.2011, p. 222-225.

Research output: Contribution to journalArticle

Qian, BZ, Li, J, Zhang, H, Kitamura, T, Zhang, J, Campion, LR, Kaiser, EA, Snyder, LA & Pollard, JW 2011, 'CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis', Nature, vol. 475, no. 7355, pp. 222-225. https://doi.org/10.1038/nature10138
Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011 Jul 14;475(7355):222-225. https://doi.org/10.1038/nature10138
Qian, Bin Zhi ; Li, Jiufeng ; Zhang, Hui ; Kitamura, Takanori ; Zhang, Jinghang ; Campion, Liam R. ; Kaiser, Elizabeth A. ; Snyder, Linda A. ; Pollard, Jeffrey W. / CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. In: Nature. 2011 ; Vol. 475, No. 7355. pp. 222-225.
@article{aefaff13324449e9bcfdfab5319f9d3d,
title = "CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis",
abstract = "Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.",
author = "Qian, {Bin Zhi} and Jiufeng Li and Hui Zhang and Takanori Kitamura and Jinghang Zhang and Campion, {Liam R.} and Kaiser, {Elizabeth A.} and Snyder, {Linda A.} and Pollard, {Jeffrey W.}",
year = "2011",
month = "7",
day = "14",
doi = "10.1038/nature10138",
language = "English (US)",
volume = "475",
pages = "222--225",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7355",

}

TY - JOUR

T1 - CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

AU - Qian, Bin Zhi

AU - Li, Jiufeng

AU - Zhang, Hui

AU - Kitamura, Takanori

AU - Zhang, Jinghang

AU - Campion, Liam R.

AU - Kaiser, Elizabeth A.

AU - Snyder, Linda A.

AU - Pollard, Jeffrey W.

PY - 2011/7/14

Y1 - 2011/7/14

N2 - Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.

AB - Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=79960411324&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960411324&partnerID=8YFLogxK

U2 - 10.1038/nature10138

DO - 10.1038/nature10138

M3 - Article

VL - 475

SP - 222

EP - 225

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7355

ER -