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Editorial

Editorial Mammary gland development and function would not be possible without tissue-specific stem cells. The mammalian reproductive cycles of pregnancy-associated proliferation, lactational differentiation, apoptosis and remodelling following weaning may occur many times during a female’s reproductive years. Such processes necessitate a population of tissue-specific stem cells that have a near unlimited capacity to generate the short-lived, differentiated breast cells. In contrast to the functional cells, breast stem cells must last throughout the life of an organism. Because of this longevity, stem cells may accumulate genetic alterations that eventually lead to cancer. This hierarchical organization of the normal epithelium is possibly reflected in the breast-cancer epithelium itself. In humans, preliminary data (in this Supplement) suggest that breast tumours contain a population with stem-cell characteristics. Current tumour therapy modalities target proliferative cells, and can be successful in causing tumour regression. However, if tumour stem cells remain at the end of treatment, tumour regrowth is likely. Targeting these tumour stem cells will be an important goal of future research. The rationale for learning more about the biology of stem cells in the mammary gland is therefore at least twofold: firstly, to understand the normal stem-cell type in which cancer is likely to be initiated, and to target such a cell in prevention therapies; and secondly, to target tumour stem cells themselves with therapies that inhibit their self-renewal activity. Many complementary approaches for the isolation and characterization of stem cells are described in this Supplement. In mice, these approaches include: (i) the transplantation of retrovirally tagged epithelial cells in order to examine their self-renewal capacity in the mammary fat pad and to analyse the repertoire of cell types produced; and (ii) the use of long-term label retention, flow cytometry and transgenic techniques to mark putative stem cells. For the human breast, isolation of populations enriched for stem cells from reduction mammoplasty specimens using antibodies to cell surface proteins, Hoechst dye efflux and stem cell-enriching culture conditions, or combinations of these methods are proving to be successful, if laborious. Advances are also being made in dissecting the signalling pathways that regulate stem-cell self-renewal, and this is obviously tremendously important if we wish to target this population of cells. In this Supplement, we present a series of review articles that address these various aspects of mammary gland stem-cell biology. The latest evidence for the presence of breast stem cells and the emerging understanding of their phenotype and regulation is discussed. Progress is clearly being made in isolating and characterizing breast stem cells, demonstrating the properties they share with stem cells in other adult tissues and describing their role in mammary gland carcinogenesis. The hope is that advancement of our current knowledge of mammary stem-cell biology will provide a roadmap for the targeting of stem cells as a therapeutic modality in the prevention and treatment of breast cancer. These articles have been subjected to peer review. The production of supplements such as this requires specific funding, and we therefore gratefully acknowledge that this Supplement is supported by an educational grant from AstraZeneca, Macclesfield. Robert B. Clarke Guest Editor © 2003 Blackwell Publishing Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cell Proliferation Wiley

Editorial

Cell Proliferation , Volume 36 (s1) – Oct 1, 2003

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Publisher
Wiley
Copyright
© 2003 Blackwell Publishing Ltd.
ISSN
0960-7722
eISSN
1365-2184
DOI
10.1046/j.1365-2184.36.s.1.1.x
Publisher site
See Article on Publisher Site

Abstract

Mammary gland development and function would not be possible without tissue-specific stem cells. The mammalian reproductive cycles of pregnancy-associated proliferation, lactational differentiation, apoptosis and remodelling following weaning may occur many times during a female’s reproductive years. Such processes necessitate a population of tissue-specific stem cells that have a near unlimited capacity to generate the short-lived, differentiated breast cells. In contrast to the functional cells, breast stem cells must last throughout the life of an organism. Because of this longevity, stem cells may accumulate genetic alterations that eventually lead to cancer. This hierarchical organization of the normal epithelium is possibly reflected in the breast-cancer epithelium itself. In humans, preliminary data (in this Supplement) suggest that breast tumours contain a population with stem-cell characteristics. Current tumour therapy modalities target proliferative cells, and can be successful in causing tumour regression. However, if tumour stem cells remain at the end of treatment, tumour regrowth is likely. Targeting these tumour stem cells will be an important goal of future research. The rationale for learning more about the biology of stem cells in the mammary gland is therefore at least twofold: firstly, to understand the normal stem-cell type in which cancer is likely to be initiated, and to target such a cell in prevention therapies; and secondly, to target tumour stem cells themselves with therapies that inhibit their self-renewal activity. Many complementary approaches for the isolation and characterization of stem cells are described in this Supplement. In mice, these approaches include: (i) the transplantation of retrovirally tagged epithelial cells in order to examine their self-renewal capacity in the mammary fat pad and to analyse the repertoire of cell types produced; and (ii) the use of long-term label retention, flow cytometry and transgenic techniques to mark putative stem cells. For the human breast, isolation of populations enriched for stem cells from reduction mammoplasty specimens using antibodies to cell surface proteins, Hoechst dye efflux and stem cell-enriching culture conditions, or combinations of these methods are proving to be successful, if laborious. Advances are also being made in dissecting the signalling pathways that regulate stem-cell self-renewal, and this is obviously tremendously important if we wish to target this population of cells. In this Supplement, we present a series of review articles that address these various aspects of mammary gland stem-cell biology. The latest evidence for the presence of breast stem cells and the emerging understanding of their phenotype and regulation is discussed. Progress is clearly being made in isolating and characterizing breast stem cells, demonstrating the properties they share with stem cells in other adult tissues and describing their role in mammary gland carcinogenesis. The hope is that advancement of our current knowledge of mammary stem-cell biology will provide a roadmap for the targeting of stem cells as a therapeutic modality in the prevention and treatment of breast cancer. These articles have been subjected to peer review. The production of supplements such as this requires specific funding, and we therefore gratefully acknowledge that this Supplement is supported by an educational grant from AstraZeneca, Macclesfield. Robert B. Clarke Guest Editor © 2003 Blackwell Publishing Ltd.

Journal

Cell ProliferationWiley

Published: Oct 1, 2003

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