Research article
Resident macrophages influence stem cell activity in the mammary gland
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* Corresponding author: Jane E Visvader visvader@wehi.edu.au
1 VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Vic 3052, Australia
2 Department of Medical Biology, The University of Melbourne, Parkville, Vic 3010, Australia
3 Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Van der Boechorstraat 7, 1081 BT, Amsterdam, The Netherlands
4 Department of Medical Oncology, The Royal Melbourne Hospital, Grattan Street, Parkville, Vic 3050, Australia
5 Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Vic 3050, Australia
Breast Cancer Research 2009, 11:R62 doi:10.1186/bcr2353
Published: 26 August 2009Abstract
Introduction
Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad.
Methods
Two different in vivo models were used to deplete macrophages from the mouse mammary fat pad, allowing us to examine the effect of macrophage deficiency on the mammary repopulating activity of MaSCs. Both the Csf1op/op mice and clodronate liposome-mediated ablation models entailed transplantation studies using the MaSC-enriched population.
Results
We show that mammary repopulating ability is severely compromised when the wild-type MaSC-enriched subpopulation is transplanted into Csf1op/op fat pads. In reciprocal experiments, the MaSC-enriched subpopulation from Csf1op/op glands had reduced regenerative capacity in a wild-type environment. Utilizing an alternative strategy for selective depletion of macrophages from the mammary gland, we demonstrate that co-implantation of the MaSC-enriched subpopulation with clodronate-liposomes leads to a marked decrease in repopulating frequency and outgrowth potential.
Conclusions
Our data reveal a key role for mammary gland macrophages in supporting stem/progenitor cell function and suggest that MaSCs require macrophage-derived factors to be fully functional. Macrophages may therefore constitute part of the mammary stem cell niche.