Journal
PROTEOMICS
Volume 11, Issue 20, Pages 4029-4039Publisher
WILEY-BLACKWELL
DOI: 10.1002/pmic.201100102
Keywords
Cell biology; Mammary stem cell niche; Plasma membrane; Secretome; Wnt10a
Funding
- National Health & Medical Research Council of Australia (NHMRC) [487922, 381413, 1016599]
- Australian Postgraduate Award
- Victorian Government Australia
- Australian Cancer Research Foundation
- Victorian Government, through Victorian Cancer Agency
- Victorian Breast Cancer Research Consortium
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The stem cell niche comprises stem cells (SCs), stromal cells, soluble factors, extracellular matrix constituents and vascular networks. The ability to identify signals that regulate SC self-renewal and differentiation is confounded by the difficulty in isolating pure SC niche components in sufficient quantities to enable their biochemical characterisation. Here, we report the extracellular (secretome) and adherent plasma membrane proteomes of three distinct epithelial cell subpopulations isolated and immortalized from the mouse mammary gland - basal and mammary stem cell (basal/MaSC), luminal progenitor (LP) and mature luminal (ML) cell lines. GeLC-MS/MS-based proteomic profiling revealed a distinct switch in components modulating Wnt and ephrin signalling, and integrin-mediated interactions amongst the three cell subpopulations. For example, expression of ephrin B2, ephrin receptors A1, and A2, as well as integrins alpha 2b1 and alpha 6b4 were shown to be enriched in basal/MaSCs, relative to LP and ML cells. Conspicuously, Wnt10a was uniquely detected in basal/MaSCs, and may modulate the canonical Wnt signalling pathway to maintain basal/MaSC activity. By contrast, non-canonical Wnt signalling might be elevated in ML cells, as evidenced by the high expression levels of Wnt5a, Wnt5b, and the transmembrane tyrosine kinase Ror2.
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