IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. Academic Article uri icon

Overview

abstract

  • High serum levels of IL-6 correlate with poor outcome in breast cancer patients. However, no data are available on the relationship between IL-6 and mammary stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in the MCF-7 breast cancer cell line and in primary human mammospheres (MS), multicellular structures enriched in stem/progenitor cells of the mammary gland. MS from node invasive breast carcinoma tissues expressed IL-6 mRNA at higher levels than did MS from matched non-neoplastic mammary glands. In addition, IL-6 mRNA was detected only in basal-like breast carcinoma tissues, an aggressive breast carcinoma variant showing stem cell features. IL-6 treatment triggered Notch-3-dependent upregulation of the Notch ligand Jagged-1 and promotion of MS and MCF-7-derived spheroid growth. Moreover, IL-6 induced Notch-3-dependent upregulation of the carbonic anhydrase IX gene and promoted a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, autocrine IL-6 signaling relied upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, these 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.

authors

  • Sansone, Pasquale
  • Storci, Gianluca
  • Tavolari, Simona
  • Guarnieri, Tiziana
  • Giovannini, Catia
  • Taffurelli, Mario
  • Ceccarelli, Claudio
  • Santini, Donatella
  • Paterini, Paola
  • Marcu, Kenneth B
  • Chieco, Pasquale
  • Bonafè, Massimiliano

publication date

  • December 1, 2007

Research

keywords

  • Breast Neoplasms
  • Carcinoma, Ductal
  • Interleukin-6
  • Mammary Glands, Human
  • Neoplasm Proteins
  • Spheroids, Cellular
  • Stem Cells

Identity

PubMed Central ID

  • PMC2096439

Scopus Document Identifier

  • 36849039660

Digital Object Identifier (DOI)

  • 10.1172/JCI32533

PubMed ID

  • 18060036

Additional Document Info

volume

  • 117

issue

  • 12