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Review
. 2003 Oct;36 Suppl 1(Suppl 1):59-72.
doi: 10.1046/j.1365-2184.36.s.1.6.x.

Stem cells in normal breast development and breast cancer

Gabriela Dontu  1 , Muhammad Al-Hajj, Wissam M Abdallah, Michael F Clarke, Max S Wicha
Affiliations
Review

Stem cells in normal breast development and breast cancer

Gabriela Dontu et al. Cell Prolif. 2003 Oct.

Abstract

The main focus of this review is the role of mammary stem cells in normal breast development and carcinogenesis. We have developed a new in vitro culture system that permits, for the first time, the propagation of mammary stem and progenitor cells in an undifferentiated state, which should facilitate the elucidation of pathways that regulate normal mammary stem-cell self-renewal and differentiation. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. A key event in this process is the deregulation of normal self-renewal in these cells. Transformed mammary stem or progenitor cells undergo aberrant differentiation processes that result in generation of the phenotypic heterogeneity found in human and rodent breast cancers. This phenotypic diversity is driven by a small subset of mammary tumour stem cells. We will discuss the important implications of this mammary tumour stem-cell model.

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Figures

Figure 1
Figure 1
Mammosphere‐derived cells have stem‐cell characteristics. (a) Mammosphere structure (15 days’ growth). Mammosphere‐derived cells plated at clonogenic denstities can (b) generate mixed colonies, containing cells of all the three mammary lineage types (ductal epithelial, ESA, brown; myoepithelial, CD10, purple; alveolar, beta‐casein, red) or (c) generate complex structures in 3D Matrigel culture. (d) The structures clonally generated in vitro are functional, as demonstrated by beta‐casein secretion (immunostained red). Self‐renewal is demonstrated by serial passages of mammospheres.
Figure 2
Figure 2
Role of stem cells in normal mammary development and carcinogenesis. Normal mammary stem cells are defined by their ability to undergo self‐renewal and to differentiate into the three cell lineages present in the mature gland. Mammary tumours arise from stem cells or progenitor cells through deregulation of normal self‐renewal. Tumour stem cells retain the ability to self‐renew as well as to differentiate. The tumorigenic stem‐cell population is maintained through self‐renewal. Aberrant differentiation of these cells generates nontumorigenic progeny, representing the bulk of the tumour.
Figure 3
Figure 3
Similarities between normal stem cells and cancer cells and their impact on stem‐cell functionality and carcinogenesis.
See this image and copyright information in PMC

References

    1. Al‐Hajj M, Wicha MS, Benito‐Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983 [Erratum in: Proc. Natl. Acad. Sci. USA 2003; 100: 6890]. - PMC - PubMed
    1. Brittan M, Wright NA (2002) Gastrointestinal stem cells. J. Pathol. 197, 492. - PubMed
    1. Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20, 11. - PubMed
    1. Caldwell MA, He X, Wilkie N, Pollack S, Marshall G, Wafford KA, Svendsen CN (2001) Growth factors regulate the survival and fate of cells derived from human neurospheres. Nature Biotech. 19, 475. - PubMed
    1. Daniel C, Young L, Medina D, Deome K (1971) The influence of mammogenic hormones on serially transplanted mouse mammary gland. Exp. Gerontol. 6, 95. - PubMed

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