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. 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.
Pece
Salvatore
S
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy. salvatore.pece@ifom-ieo-campus.it
Tosoni
Daniela
D
Confalonieri
Stefano
S
Mazzarol
Giovanni
G
Vecchi
Manuela
M
Ronzoni
Simona
S
Bernard
Loris
L
Viale
Giuseppe
G
Pelicci
Pier Giuseppe
PG
Di Fiore
Pier Paolo
PP
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002469:Cell Separation; D004848:Epithelium / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*