Interleukin-1β regulates the migratory potential of MDAMB231 breast cancer cells through the hypoxia-inducible factor-1α

Antonella Naldini, Irene Filippi, Diego Miglietta, Michele Moschetta, Raffaella Giavazzi, Fabio Carraro

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The casual relationship between inflammation and tumour progression has been widely accepted and the etiology of breast cancer has been associated with inflammatory processes. Interleukin (IL)-1β, besides its central role in inflammation, has also been recognised as a powerful player in tumour progression, angiogenesis and invasiveness. Recently, there has been considerable interest in understanding the non-hypoxic upregulation of the hypoxia-inducible factor (HIF)-1α by IL-1 in neoplastic cells since aberrant expression of HIF-1α correlates with tumour progression. Here, using the highly invasive human breast cancer cell line MDAMB231, we studied the effect of IL-1β on tumour cell migration along with HIF-1α accumulation. We observed that non-hypoxic induction of HIF-1α by IL-1β in MDAMB231 was associated with increased cell migration, paralleled by upregulation of p38 MAPK phosphorylation and CXCL8/CXCR1 expression. Inhibition of HIF-1α by siRNA resulted in a significant reduction of CXCR1 expression and IL-1β-induced cell migration in MDAMB231 cells, thus confirming a role of HIF-1α in the non-hypoxic-IL-1β-dependent induction of migratory potentials. Our observation that IL-1 induces HIF-1α accumulation in MDAMB231 cells was confirmed in tumour cells growing in vivo using an experimental approach, mimicking the endogenous release of IL-1 in mice bearing MDAMB231 xenografts. Our in vivo data, along with the fact that inhibition of HIF-1α resulted in the decrease of IL-1β-promoted cell migration, further support the link between inflammation and cancer. The overall results may have important implications in those therapeutic approaches aimed to inhibit IL-1-mediated activities in tumour cells, specifically in breast cancer.

Original languageEnglish
Pages (from-to)3400-3408
Number of pages9
JournalEuropean Journal of Cancer
Volume46
Issue number18
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Hypoxia-Inducible Factor 1
Cell Hypoxia
Interleukin-1
Breast Neoplasms
Cell Movement
Neoplasms
Inflammation
Up-Regulation
p38 Mitogen-Activated Protein Kinases
Heterografts
Small Interfering RNA
Phosphorylation

Keywords

  • Breast cancer
  • Cell migration
  • CXCL8
  • HIF-1α
  • IL-1β

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interleukin-1β regulates the migratory potential of MDAMB231 breast cancer cells through the hypoxia-inducible factor-1α. / Naldini, Antonella; Filippi, Irene; Miglietta, Diego; Moschetta, Michele; Giavazzi, Raffaella; Carraro, Fabio.

In: European Journal of Cancer, Vol. 46, No. 18, 12.2010, p. 3400-3408.

Research output: Contribution to journalArticle

Naldini, Antonella ; Filippi, Irene ; Miglietta, Diego ; Moschetta, Michele ; Giavazzi, Raffaella ; Carraro, Fabio. / Interleukin-1β regulates the migratory potential of MDAMB231 breast cancer cells through the hypoxia-inducible factor-1α. In: European Journal of Cancer. 2010 ; Vol. 46, No. 18. pp. 3400-3408.
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