Cancer stem cell heterogeneity in hereditary breast cancer

Max S Wicha

doi:10.1186/bcr1990

Abstract

The cancer stem cell hypothesis proposes that tumors arise in stem or progenitor cells generating in tumors driven by a subcomponent that retains cancer stem cell properties. Recent evidence supports the hypothesis that the BRCA1 gene involved in hereditary breast cancer plays a role in breast stem cell function. Furthermore, studies using mouse BRCA1 knockout models provide evidence for the existence of heterogeneous cancer stem cell populations in tumors generated in these mice. Although these populations may arise from different stem/progenitor cells, they share the expression of a common set of stem cell regulatory genes and show similar characteristics in in vitro mammosphere assays and xenograft models. Furthermore, these 'cancer stem cells' display resistance to chemotherapeutic agents. These studies suggest that breast tumors may display intertumor stem cell heterogeneity. Despite this heterogeneity, cancer stem cells may share common characteristics that can be used for their identification and for therapeutic targeting.

Highlights

In a recent publication, Wright and colleagues [1] used a mouse knockout model of BRCA1 to demonstrate cellular heterogeneity of cancer stem cells
Cells derived from one tumor contained populations that were characterized as CD44+/ CD24– and that displayed stem cell properties, whereas cells derived from another tumor contained a cancer stem cell population that was characterized by CD133 expression
The CD44+/CD24– phenotype previously has been described as identifying a cell population with stem cell properties in human breast tumors [2]

Summary

Introduction

Wright and colleagues [1] used a mouse knockout model of BRCA1 to demonstrate cellular heterogeneity of cancer stem cells. The CD44+/CD24– phenotype previously has been described as identifying a cell population with stem cell properties in human breast tumors [2]. Sheridan and colleagues [3] recently reported that a number of basal mammary carcinoma cell lines contain a CD44+/CD24– cell population, whereas luminal cell lines do not.

Results

Conclusion