TY - JOUR
T1 - Resident macrophages influence stem cell activity in the mammary gland
AU - Gyorki, David E.
AU - Asselin-Labat, Marie Liesse
AU - van Rooijen, Nico
AU - Lindeman, Geoffrey J.
AU - Visvader, Jane E.
N1 - Funding Information:
We are grateful to S. Holroyd and K. Haunholter for expert technical assistance, to K. Stoev and K. Johnson for excellent animal husbandry, and S. Mihajlovic and E. Tsui for expert assistance with histology. R. Anderson kindly provided the BALB/c Csf1op/opmice. We thank John Hamilton for discussions. This work was supported by the Victorian Breast Cancer Research Consortium, National Health and Medical Research Council (NHMRC, Australia). D. Gyorki received support from the National Health and Medical Research Council, Royal Australasian College of Surgeons and the National Breast Cancer Foundation. M-L Asselin-Labat was the recipient of an ARC Fellowship (Australia).
PY - 2009/8/26
Y1 - 2009/8/26
N2 - 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.
AB - 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.
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U2 - 10.1186/bcr2353
DO - 10.1186/bcr2353
M3 - Article
C2 - 19706193
AN - SCOPUS:72749084487
SN - 1465-5411
VL - 11
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 4
M1 - R62
ER -