• The role of interleuchin 6 (IL-6) in the promotion of an aggressive and stem cell-like phenotype in human breast cancer cells and in stem/progenitor cells expanded in vitro as mammospheres
  • La citochina pro-infiammatoria IL-6 promuove un fenotipo aggressivo e staminale in cellule di carcinoma mammario umano
  • Sansone, Pasquale <1981>

Subject

  • BIO/14 Farmacologia

Description

  • 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.

Date

  • 2009-03-24

Type

  • Doctoral Thesis
  • PeerReviewed

Format

  • application/pdf

Identifier

http://amsdottorato.unibo.it/2087/1/sansone_pasquale_tesi.pdf

urn:nbn:it:unibo-1637

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.

Relations

http://amsdottorato.unibo.it/2087/