Interleukin-1β Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1α and NFκB Transcription Factors

Abstract

Inflammation and tumor hypoxia are intimately linked and breast cancer provides a typical example of an inflammation-linked malignant disease. Indeed, breast cancer progression is actively supported by inflammatory components, including IL-1β, and by the hypoxia-inducible factor- (HIF-) 1α. In spite of many attempts where the role of either IL-1β or HIF-1α was evaluated, detailed mechanisms for their effects on breast cancer cell migration under hypoxia are still unclear. We here report that IL-1β increased MDAMB231 cell migration under hypoxic conditions along with HIF-1α accumulation and upregulation of CXCR1, which is transcriptionally regulated by HIF-1α, as well as an increased expression of CXCL8 and NFκB. In addition, IL-1β-induced cell migration in hypoxia was not affected when HIF-1α was inhibited by either siRNA or Topotecan, well known for its inhibitory effect on HIF-1α. Of interest, HIF-1α inhibition did not reduce NFκB and CXCL8 expression and the reduction of IL-1β-induced cell migration under hypoxia was achieved only by pharmacological inhibition of NFκB. Our findings indicate that inhibition of HIF-1α does not prevent the migratory program activated by IL-1β in hypoxic MDAMB231 cells. They also suggest a potential compensatory role of NFκB/CXCL8 pathway in IL-1β-induced MDAMB231 cell migration in a hypoxic microenvironment.