Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate.
There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type by oncogenic insults, or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in Dana-Farber Cancer Institute 1 (DFCI-1) medium retain a fraction with progenitor cell properties. These cells coexpress basal (K5, K14, and vimentin), luminal (E-cadherin, K8, K18, or K19), and stem/progenitor (CD49f, CD29, CD44, and p63) cell markers. Clonal derivatives of progenitors coexpressing these markers fall into two distinct types--a K5(+)/K19(-) type and a K5(+)/K19(+) type. We show that both types of progenitor cells have self-renewal and differentiation ability. Microarray analyses confirmed the differential expression of components of stem/progenitor-associated pathways, such as Notch, Wnt, Hedgehog, and LIF, in progenitor cells compared with differentiated cells. Given the emerging evidence that stem/progenitor cells serve as precursors for cancers, these cellular reagents represent a timely and invaluable resource to explore unresolved questions related to stem/progenitor origin of breast cancer.
Zhao
Xiangshan
X
Department of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Malhotra
Gautam K
GK
Lele
Subodh M
SM
Lele
Manjiri S
MS
West
William W
WW
Eudy
James D
JD
Band
Hamid
H
Band
Vimla
V
D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line / Q000166:cytology*; D049109:Cell Proliferation; D002999:Clone Cells / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D042361:Mammary Glands, Human / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D019098:Telomerase
D015415:Biomarkers; D019098:Telomerase