Mammosphere-forming cells from breast cancer cell lines as a tool for the identification of CSC-like- and early progenitor-targeting drugs.
Here we show that a subpopulation of MCF-7 breast cancer cells which stains pale to Toluidine Blue (Light Cells- LCs), is endowed with features of CSCs. LCs give rise to self-renewing mammospheres and express typical CSC markers; moreover this subpopulation is chemoresistant and highly tumorigenic in vivo. LCs can be identified in several other breast cancer cell lines, irrespectively of their histological origin (luminal vs. mesenchymal vs. basal) and represent an heterogeneous cell population composed mainly of CSC-like and early progenitor cells. By a limited in vitro drug screening assay, we identify compounds which can specifically interfere with the viability of LCs from multiple breast cancer cell lines. Analysis of the Sphere-Forming Efficiency (SFE) and of the distribution of ALDH(bright) cells within the treated cell lines suggest that one of the identified compounds acts in vitro by modulating the CSC phenotype. Interestingly, a subset of the identified compounds is known to affect directly or indirectly the NFkappaB pathway which is emerging as an important modulator of CSC proliferation and chemoresistance.
Cioce
Mario
M
Department of Molecular Medicine, Regina Elena Cancer Institute, Rome, Italy. mcioce@ifo.it
Gherardi
Simona
S
Viglietto
Giuseppe
G
Strano
Sabrina
S
Blandino
Giovanni
G
Muti
Paola
P
Ciliberto
Gennaro
G
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D014048:Tolonium Chloride / Q000494:pharmacology
D016328:NF-kappa B; D014048:Tolonium Chloride