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

  • Gabriela Dontu
  • Max S. Wicha
Article

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.

stem cells cancer stem cells breast cancer mammary gland development Wnt signaling self-renewal differentiation 

Abbreviations used

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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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Internal Medicine, Hematology–Oncology, Comprehensive Cancer CenterUniversity of MichiganAnn Arbor
  2. 2.Ann Arbor

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