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  • PPARγ and RXR ligands disrupt the inflammatory cross-talk in the hypoxic breast cancer stem cells niche.

PPARγ and RXR ligands disrupt the inflammatory cross-talk in the hypoxic breast cancer stem cells niche.

Journal of cellular physiology (2014-03-08)
Alessio Papi, Sabrina De Carolis, Sara Bertoni, Gianluca Storci, Virginia Sceberras, Donatella Santini, Claudio Ceccarelli, Mario Taffurelli, Marina Orlandi, Massimiliano Bonafé
ABSTRACT

Cancer stem cells (CSCs) are affected by the local micro-environment, the niche, in which inflammatory stimuli and hypoxia act as steering factors. Here, two nuclear receptors (NRs) agonists, i.e. pioglitazone (PGZ), a ligand of peroxisome proliferator activated receptor-γ, and 6-OH-11-O-hydroxyphenanthrene (IIF), a ligand of retinoid X receptors, were investigated for their capability to interference with the cross-talk between breast CSCs and the niche compartment. We found that IIF potentiates the ability of PGZ to hamper the mammospheres-forming capability of human breast tumours and MCF7 cancer cells, reducing the expression of CSCs regulatory genes (Notch3, Jagged1, SLUG, Interleukin-6, Apolipoprotein E, Hypoxia inducible factor-1α and Carbonic anhydrase IX). Notably, these effects are not observed in normal-MS obtained from human breast tissue. Importantly, NRs agonists abolish the capability of hypoxic MCF7 derived exosomes to induce a pro-inflammatory phenotype in mammary glands fibroblasts. Moreover, NRs agonist also directly acts on breast tumour associated fibroblasts to downregulate nuclear factor-κB pathway and metalloproteinases (MMP2 and MMP9) expression and activity. In conclusion, NRs agonists disrupt the inflammatory cross-talk of the hypoxic breast CSCs niche.

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Carbonic Anhydrase Isozyme II from bovine erythrocytes, lyophilized powder, ≥3,000 W-A units/mg protein
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Carbonic Anhydrase Isozyme II from bovine erythrocytes, Isoelectric focusing marker, pI 5.4
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Carbonic Anhydrase Isozyme II human, ≥80%, powder, ≥3,000 W-A units/mg protein
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Carbonic Anhydrase Isozyme II from bovine erythrocytes, lyophilized powder, ≥2,000 W-A units/mg protein
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Pioglitazone for system suitability, European Pharmacopoeia (EP) Reference Standard
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Carbonic Anhydrase from bovine erythrocytes, non-denaturing PAGE marker
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Carbonic Anhydrase from bovine erythrocytes, For use as a marker in SDS-PAGE
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Carbonic Anhydrase I from human erythrocytes
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Carbonic Anhydrase I from human erythrocytes, Isoelectric focusing marker, pI 6.6
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Pioglitazone hydrochloride, United States Pharmacopeia (USP) Reference Standard
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Carbonic Anhydrase from bovine erythrocytes, ≥95% (SDS-PAGE), specific activity ≥3,500 W-A units/mg protein, lyophilized powder
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Pioglitazone hydrochloride, ≥98% (HPLC)
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Pioglitazone hydrochloride, European Pharmacopoeia (EP) Reference Standard
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₩283,490