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

Filippi, I., Carraro, F., Naldini, A. (2015). Interleukin-1β Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1αand NFκB Transcription Factors. MEDIATORS OF INFLAMMATION, 2015(2015), 1-10 [10.1155/2015/789414].

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

Filippi, Irene;Carraro, Fabio;Naldini, Antonella
2015-01-01

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 beta, and by the hypoxia-inducible factor- (HIF-) 1 alpha In spite of many attempts where the role of either IL-1 beta or HIF-1 beta was evaluated, detailed mechanisms for their effects on breast cancer cell migration under hypoxia are still unclear. We here report that IL-1 beta increased MDAMB231 cell migration under hypoxic conditions along with HIF-1 alpha accumulation and upregulation of CXCR1, which is transcriptionally regulated by HIF-1 alpha, as well as an increased expression of CXCL8 and NF kappa B. In addition, IL-1 beta-induced cell migration in hypoxia was not affected when HIF-1 alpha was inhibited by either siRNA or Topotecan, well known for its inhibitory effect on HIF-1 alpha Of interest, HIF-1 alpha inhibition did not reduce NF kappa B and CXCL8 expression and the reduction of IL-1 beta-induced cell migration under hypoxia was achieved only by pharmacological inhibition of NF kappa B. Our findings indicate that inhibition of HIF-1 alpha does not prevent the migratory program activated by IL-1 beta in hypoxic MDAMB231 cells. They also suggest a potential compensatory role of NF kappa B/CXCL8 pathway in IL-1 beta-induced MDAMB231 cell migration in a hypoxic microenvironment.
2015
Filippi, I., Carraro, F., Naldini, A. (2015). Interleukin-1β Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1αand NFκB Transcription Factors. MEDIATORS OF INFLAMMATION, 2015(2015), 1-10 [10.1155/2015/789414].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/982533