Reconstruction of human mammary tissues in a mouse model

Proia, David A.; Kuperwasser, Charlotte

doi:10.1038/nprot.2006.31

Cited by 126 publications

(118 citation statements)

References 11 publications

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“…To circumvent this, an alternative assay in which human mammary fibroblasts are injected into cleared mammary fat pads prior to implantation of the human mammary epithelial cells (HMECs) has been developed [45,46]. This assay has demonstrated that histologically normal-looking human mammary epithelial outgrowths, complete with luminal and myoepithelial cells, can be obtained when single cell suspensions of human mammary epithelial cells are transplanted into humanized mouse mammary fat pads, even from very low numbers of input cells [40,47,48].…”

Section: In Vivo Models To Detect Human Mascsmentioning

confidence: 99%

Detection and analysis of mammary gland stem cells

Stingl

2008

The Journal of Pathology

138

154

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Emerging evidence from a variety of tissue types, including the mammary gland, suggests that normal stem and progenitor cells are the likely targets for malignant transformation, and that these transformed cells can function as cancer stem cells that drive tumour growth. In order to develop therapies that target these cancer stem cells, it is essential to determine the molecular mechanisms that regulate the growth and differentiation of these cells and their normal counterparts. To this end, a number of quantitative robust clonal assays have been developed that can detect the presence of human and mouse mammary stem and progenitor cells. These assays, when used in conjunction with cell-sorting strategies, have permitted the prospective isolation and characterization of a variety of cell types, including stem cells. Evidence to date indicates that these stem cells exhibit properties of basal mammary cells, possess extensive self-renewal properties, and are capable of generating a large number of phenotypically-distinct progenitor cells, many of which display characteristics of luminal cells. This review article will focus on the assays used to detect mammary stem and progenitor cells, some of the properties of these cells and their progeny and how they relate to the cancer stem cells that drive breast tumour growth.

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Section: In Vivo Models To Detect Human Mascsmentioning

confidence: 99%

Detection and analysis of mammary gland stem cells

Stingl

2008

The Journal of Pathology

138

154

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“…Finally, sorted CD10 + and EpCAM + cells were injected in vivo to evaluate their outgrowth competency in the HIM model (13,14). Although EpCAM + and CD10 + cells exhibited differential activities in vitro, within the humanized cleared fat-pad system, cells from both the CD10 + and EpCAM + populations could generate bilayered mammary outgrowths comprised of an inner luminal epithelial layer that expressed CK8/18 and CK19 and an outer epithelial layer that expressed CK14 (Fig.…”

Section: Characterization Of Breast Epithelial Cell Properties In Hummentioning

confidence: 99%

“…Thus, it remains unknown whether all human breast tumors are derived from the same cellular precursors or whether different cell types contribute to the heterogeneity of breast cancers. In this study, we sought to examine the relationship between luminal and basal/ME cells and breast cancer subtypes through use of the recently described human-in-mouse (HIM) model (13,14). With this approach, we discovered unique properties of a cell population within human mammary basal/ME epithelial cells that provide important insights into the origins of rare breast cancers.…”

mentioning

confidence: 99%

Defining the cellular precursors to human breast cancer

Keller

Arendt

Skibinski

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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185

216

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Human breast cancers are broadly classified based on their geneexpression profiles into luminal-and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM + ) and basal/myoepithelial (CD10 + ). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM + epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10 + cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10 + breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.cell of origin | epidermal progenitor cells | luminal progenitors

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“…The fact that the human cells are growing in an immunodeficient mouse environment constitute obvious shortcomings of these approaches. New models have been developed in which human fibroblasts were transplanted together with the neoplastic cells, thus creating a humanized environment, although the possible role of the immune system has not been yet properly addressed (Proia & Kuperwasser 2006).…”

Section: Xenografts In Immunodeficient Animalsmentioning

confidence: 99%

The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

Lanari¹,

Lamb²,

Fabris³

et al. 2009

Endocrine-Related Cancer

101

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More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.

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Reconstruction of human mammary tissues in a mouse model

Cited by 126 publications

References 11 publications

Detection and analysis of mammary gland stem cells

Detection and analysis of mammary gland stem cells

Defining the cellular precursors to human breast cancer

The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

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