Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 62-73 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 140 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 8 2010 |
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Keywords
- HUMDISEASE
- PROTEINS
- STEMCELL
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content. / Pece, Salvatore; Tosoni, Daniela; Confalonieri, Stefano; Mazzarol, Giovanni; Vecchi, Manuela; Ronzoni, Simona; Bernard, Loris; Viale, Giuseppe; Pelicci, Pier Giuseppe; Di Fiore, Pier Paolo.
In: Cell, Vol. 140, No. 1, 08.01.2010, p. 62-73.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content
AU - Pece, Salvatore
AU - Tosoni, Daniela
AU - Confalonieri, Stefano
AU - Mazzarol, Giovanni
AU - Vecchi, Manuela
AU - Ronzoni, Simona
AU - Bernard, Loris
AU - Viale, Giuseppe
AU - Pelicci, Pier Giuseppe
AU - Di Fiore, Pier Paolo
PY - 2010/1/8
Y1 - 2010/1/8
N2 - 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.
AB - 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.
KW - HUMDISEASE
KW - PROTEINS
KW - STEMCELL
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UR - http://www.scopus.com/inward/citedby.url?scp=73149110562&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2009.12.007
DO - 10.1016/j.cell.2009.12.007
M3 - Article
C2 - 20074520
AN - SCOPUS:73149110562
VL - 140
SP - 62
EP - 73
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -