Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content

Pathways that govern stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SCs (hNMSCs), from cultured mammospheres, on the basis of their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. PKH2...

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Bibliographic Details
Published in:Cell 2010-01, Vol.140 (1), p.62-73
Main Authors: Pece, Salvatore, Tosoni, Daniela, Confalonieri, Stefano, Mazzarol, Giovanni, Vecchi, Manuela, Ronzoni, Simona, Bernard, Loris, Viale, Giuseppe, Pelicci, Pier Giuseppe, Di Fiore, Pier Paolo
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - pathology
Cell Separation
Epithelium - pathology
Female
Flow Cytometry
Gene Expression Profiling
Humans
HUMDISEASE
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells - pathology
PROTEINS
STEMCELL
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Summary:Pathways that govern stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SCs (hNMSCs), from cultured mammospheres, on the basis of their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we prospectively isolated SCs from the normal gland and from breast tumors. Poorly differentiated (G3) cancers displayed higher content of prospectively isolated cancer SCs (CSCs) than did well-differentiated (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in CSCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their CSC content. [Display omitted] ► Human mammary stem cells (hNMSCs) can be isolated to a high degree of purity ► hNMSCs have a distinctive molecular signature ► The signature distinguishes breast cancers of different grades and molecular subtypes ► Breast cancer stem cell content relates to degree of differentiation and prognosis
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2009.12.007