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PMID: 16300651 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Isolation and characterization of human mammary stem cells.

Cell proliferation ·Vol. 38 ·No. 6 ·2005-12-00 ·Pages 375-86

Clarke RB

Abstract

Since stem cells are present throughout the lifetime of an organism, it is thought that they may accumulate mutations, eventually leading to cancer. In the breast, tumours are predominantly oestrogen and progesterone receptor-positive (ERalpha/PR+). We therefore studied the biology of ERalpha/PR-positive cells and their relationship to stem cells in normal human mammary epithelium. We demonstrated that ERalpha/PR-positive cells co-express the putative stem cell markers p21(CIP1/WAF1), cytokeratin (CK) 19 and Musashi-1 when examined using dual label immunofluorescence on tissue sections. Next, we isolated a Hoechst dye-effluxing 'side population' (SP) from the epithelium using flow cytometry and demonstrated them to be undifferentiated cells by lack of expression of myoepithelial and luminal cell-specific antigens such as CALLA and MUC1. Epithelial SP cells were shown to be enriched for the putative stem cell markers p21(CIP1/WAF1), Musashi-1 and ERalpha/PR-positive cells. Lastly, SP cells, compared to non-SP, were highly enriched for the capacity to produce colonies containing multiple lineages in 3D basement membrane (Matrigel) culture. We conclude that breast stem cells include two populations: a primitive ERalpha/PR-negative stem cell necessary for development and a shorter term ERalpha/PR-positive stem cell necessary for adult tissue homeostasis during menstrual cycling. We speculate these two basic stem cell types may therefore be the cells of origin for ERalpha-positive and -negative breast tumours.

MeSH Terms
Breast/cytology,metabolism,physiology Cell Separation/methods Female Humans Stem Cells/cytology,metabolism,physiology
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Clarke R B
Breast Biology Group, Division of Cancer Studies, University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK. robert.clarke@manchester.ac.uk
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Article Info
Journal
Cell proliferation
Abbr.
Cell Prolif
ISSN
0960-7722
DOI
10.1111/j.1365-2184.2005.00357.x
Email
robert.clarke@manchester.ac.uk
Published
2005-12-00
Pages
375-86
Language
English
Region
England
NLM ID
9105195
PMCID
PMC6495923
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2184.2005.00357.x PMC Full Text View journal details
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