Interleukin-1? Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1? and NF?B 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-1?, and by the hypoxia-inducible factor- (HIF-) 1?. In spite of many attempts where the role of either IL-1? or HIF-1? was evaluated, detailed mechanisms for their effects on breast cancer cell migration under hypoxia are still unclear. We here report that IL-1? increased MDAMB231 cell migration under hypoxic conditions along with HIF-1? accumulation and upregulation of CXCR1, which is transcriptionally regulated by HIF-1?, as well as an increased expression of CXCL8 and NF?B. In addition, IL-1?-induced cell migration in hypoxia was not affected when HIF-1? was inhibited by either siRNA or Topotecan, well known for its inhibitory effect on HIF-1?. Of interest, HIF-1? inhibition did not reduce NF?B and CXCL8 expression and the reduction of IL-1?-induced cell migration under hypoxia was achieved only by pharmacological inhibition of NF?B. Our findings indicate that inhibition of HIF-1? does not prevent the migratory program activated by IL-1? in hypoxic MDAMB231 cells. They also suggest a potential compensatory role of NF?B/CXCL8 pathway in IL-1?-induced MDAMB231 cell migration in a hypoxic microenvironment.

SUBMITTER: Filippi I 

PROVIDER: S-EPMC4677223 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature