Recent literature highlights the importance of pro-inflammatory cytokines in the biology of breast cancer stem cells, unravelling differences with respect to their normal counterparts. Expansion of mammospheres is a valuable tool for the in vitro study of normal and cancer mammary gland stem cells. Here, we expanded mammospheres from human breast cancer and normal mammary gland tissues, as well from tumorigenic (MCF7) and non tumorigenic (MCF10) breast cell lines. We observed that agonists for the retinoid X receptor (6-OH-hydroxidrofenantrene), retinoic acid receptor (all-trans retinoic acid) and peroxisome proliferator-activated receptor (PPAR)-γ (pioglitazone), reduce the survival of mammospheres generated from breast cancer tissues and MCF7 cells, but not from normal mammary gland or MCF10 cells. This phenomenon is paralleled by the hampering of pro-inflammatory Nuclear Factor-κB/Interleukin-6 axis that is hyperactive in breast cancer-derived mammospheres. The hindrance of such pathway associates with the down-regulation of mammospheres regulatory genes (SLUG, Notch3, Jagged1) and with the up-regulation of the differentiation markers estrogen receptor-α and keratin18. At variance, the PPARα agonist Wy14643 promotes mammospheres formation, up-regulating Nuclear Factor-κB/Interleukin-6 axis and mammosphere regulatory genes. These data reveal that nuclear receptors agonists (6-OH-hydroxidrofenantrene, all-trans retinoic acid, pioglitazone) reduce the inflammation dependent survival of breast cancer stem cells and that PPARα agonist Wy14643 exerts opposite effects on this phenotype.
Nuclear receptors agonists exert opposing effects on the inflammation-dependent survival of breast cancer stem cells.
PAPI, ALESSIO;GUARNIERI, TIZIANA;STORCI, GIANLUCA;SANTINI, DONATELLA;CECCARELLI, CLAUDIO;TAFFURELLI, MARIO;ORLANDI, MARINA;BONAFE', MASSIMILIANO
2012
Abstract
Recent literature highlights the importance of pro-inflammatory cytokines in the biology of breast cancer stem cells, unravelling differences with respect to their normal counterparts. Expansion of mammospheres is a valuable tool for the in vitro study of normal and cancer mammary gland stem cells. Here, we expanded mammospheres from human breast cancer and normal mammary gland tissues, as well from tumorigenic (MCF7) and non tumorigenic (MCF10) breast cell lines. We observed that agonists for the retinoid X receptor (6-OH-hydroxidrofenantrene), retinoic acid receptor (all-trans retinoic acid) and peroxisome proliferator-activated receptor (PPAR)-γ (pioglitazone), reduce the survival of mammospheres generated from breast cancer tissues and MCF7 cells, but not from normal mammary gland or MCF10 cells. This phenomenon is paralleled by the hampering of pro-inflammatory Nuclear Factor-κB/Interleukin-6 axis that is hyperactive in breast cancer-derived mammospheres. The hindrance of such pathway associates with the down-regulation of mammospheres regulatory genes (SLUG, Notch3, Jagged1) and with the up-regulation of the differentiation markers estrogen receptor-α and keratin18. At variance, the PPARα agonist Wy14643 promotes mammospheres formation, up-regulating Nuclear Factor-κB/Interleukin-6 axis and mammosphere regulatory genes. These data reveal that nuclear receptors agonists (6-OH-hydroxidrofenantrene, all-trans retinoic acid, pioglitazone) reduce the inflammation dependent survival of breast cancer stem cells and that PPARα agonist Wy14643 exerts opposite effects on this phenotype.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
