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.

Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content / S. Pece, D. Tosoni, S. Confalonieri, G. Mazzarol, M. Vecchi, S. Ronzoni, L. Bernard, G. Viale, P.G. Pelicci, P.P. Di Fiore. - In: CELL. - ISSN 0092-8674. - 140:14(2010), pp. 62-73. [10.1016/j.cell.2009.12.007]

Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content

S. Pece;G. Viale;P.G. Pelicci;P.P. Di Fiore
2010

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.
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Pece Cell.pdf

non disponibili

Descrizione: Full article
Tipologia: Publisher's version/PDF
Dimensione 1.76 MB
Formato Adobe PDF
1.76 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/73093
Citazioni
  • ???jsp.display-item.citation.pmc??? 412
  • Scopus 680
  • ???jsp.display-item.citation.isi??? 642
social impact