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A Progesterone-CXCR4 Axis Controls Mammary Progenitor Cell Fate in the Adult Gland.
- Source :
- Stem cell reports; vol 4, iss 3, 313-322; 2213-6711
- Publication Year :
- 2015
-
Abstract
- Progesterone drives mammary stem and progenitor cell dynamics through paracrine mechanisms that are currently not well understood. Here, we demonstrate that CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial instructor of hormone-induced mammary stem and progenitor cell function. Progesterone elicits specific changes in the transcriptome of basal and luminal mammary epithelial populations, where CXCL12 and CXCR4 represent a putative ligand-receptor pair. In situ, CXCL12 localizes to progesterone-receptor-positive luminal cells, whereas CXCR4 is induced in both basal and luminal compartments in a progesterone-dependent manner. Pharmacological inhibition of CXCR4 signaling abrogates progesterone-directed expansion of basal (CD24+CD49fhi) and luminal (CD24+CD49flo) subsets. This is accompanied by a marked reduction in CD49b+SCA-1- luminal progenitors, their functional capacity, and lobuloalveologenesis. These findings uncover CXCL12 and CXCR4 as novel paracrine effectors of hormone signaling in the adult mammary gland, and present a new avenue for potentially targeting progenitor cell growth and malignant transformation in breast cancer.
Details
- Database :
- OAIster
- Journal :
- Stem cell reports; vol 4, iss 3, 313-322; 2213-6711
- Notes :
- application/pdf, Stem cell reports vol 4, iss 3, 313-322 2213-6711
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1287363838
- Document Type :
- Electronic Resource