La citochina pro-infiammatoria IL-6 promuove un fenotipo aggressivo e staminale in cellule di carcinoma mammario umano

Sansone, Pasquale (2009) La citochina pro-infiammatoria IL-6 promuove un fenotipo aggressivo e staminale in cellule di carcinoma mammario umano, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Farmacologia e tossicologia, 21 Ciclo. DOI 10.6092/unibo/amsdottorato/2087.
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High serum levels of Interleukin-6 (IL-6) correlate with poor outcome in breast cancer patients. However no data are available on the relationship between IL-6 and stem/progenitor cells which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in mammospheres (MS), multi-cellular structures enriched in stem/progenitor cells of the mammary gland, and also in MCF-7 breast cancer cells. We show that MS from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. We find that IL-6 mRNA is detectable only in basal-like breast carcinoma tissues, an aggressive variant showing stem cell features. Our results reveal that IL-6 triggers a Notch-3-dependent up-regulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and MCF-7 derived spheroids. Moreover, IL-6 induces a Notch-3-dependent up-regulation of the carbonic anhydrase IX gene, which promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, an autocrine IL-6 loop relies upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3 expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.

Tipologia del documento
Tesi di dottorato
Sansone, Pasquale
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
IL-6 carcinoma mammario
Data di discussione
24 Marzo 2009

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