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


RESULTS
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.


CONCLUSIONS
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.
Qian
Binzhi
B
Department of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Woman's Health, Center for the Study of Reproductive Biology and Woman's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Deng
Yan
Y
Im
Jae Hong
JH
Muschel
Ruth J
RJ
Zou
Yiyu
Y
Li
Jiufeng
J
Lang
Richard A
RA
Pollard
Jeffrey W
JW
D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D002455:Cell Division / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology*
D039481:CD11b Antigen