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Survival of Mammary Stem Cells in Suspension Culture: Implications for Stem Cell Biology and Neoplasia

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Abstract

There is increasing evidence that a variety of neoplasms including breast cancer may result from transformation of normal stem and progenitor cells. In the past, isolation and characterization of mammary stem cells has been limited by the lack of suitable culture systems able to maintain these cells in an undifferentiated state in vitro. We have recently described a culture system in which human mammary stem and progenitor cells are able to survive in suspension and produce spherical colonies composed of both stem and progenitor cells. Recent observation that adult stem cells from other tissues may also retain the capacity for growth under anchorage independent conditions suggests a common underlying mechanism. We propose that this mechanism involves the interaction between the canonical Wnt signal pathway and E-cadherin. The Wnt pathway has been implicated in normal stem cell self-renewal in vivo. Furthermore, there is evidence that deregulation of this pathway in the mammary gland and other organs may play a key role in carcinogenesis. Thus, the development of in vitro suspension culture systems not only provides an important new tool for the study of mammary cell biology, but also may have important implications for understanding key molecular pathways in both normal and neoplastic stem cells.

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Abbreviations

ASMA:

alpha smooth muscle actin

APC:

adenomatosis polyposis coli

BCRP:

breast cancer resistance protein

BMI:

B-lymphoma MO-MLV insertion region 1

BMP4:

bone morhogenetic protein 4

EGF:

epidermal growth factor

ESA:

epithelial specific antigen

ER:

estrogen receptor

FACS:

fluorescence-activated cell sorting

FITC:

fluorescein isothyocyanate

bFGF:

basic fibroblast growth factor

LIF:

leukemia inhibitory factor

Muc 1:

mucin 1

MMP7:

matrix metalloproteinase 7

MTA3:

metastasis associated gene 3

NuRD:

Nuclear remodeling and deacetylation complex

PR:

progesterone receptor

PTEN:

phosphatase and tensin homolog

SP:

side population

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Authors and Affiliations

  1. Department of Internal Medicine, Hematology–Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan

    Gabriela Dontu & Max S. Wicha

  2. 1500 E Medical Center Dr., 7110 CCGC, Ann Arbor, Michigan, 48109

    Gabriela Dontu

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  1. Gabriela Dontu
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  2. Max S. Wicha
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Correspondence to Gabriela Dontu.

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Dontu, G., Wicha, M.S. Survival of Mammary Stem Cells in Suspension Culture: Implications for Stem Cell Biology and Neoplasia. J Mammary Gland Biol Neoplasia 10, 75–86 (2005). https://doi.org/10.1007/s10911-005-2542-5

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