期刊
EUROPEAN JOURNAL OF CANCER
卷 46, 期 18, 页码 3400-3408出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2010.07.044
关键词
IL-1 beta; HIF-1 alpha; CXCL8; Cell migration; Breast cancer
类别
资金
- MIUR
- PAR
- University of Siena
- Fondazione MPS
- Istituto Toscano Tumori [ITT 2008]
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Cariplo
- EU [HEALTH-F2-2008-201342]
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)-1 beta, 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)-1 alpha by IL-1 in neoplastic cells since aberrant expression of HIP-la correlates with tumour progression. Here, using the highly invasive human breast cancer cell line MDAMB231, we studied the effect of IL-1 beta on tumour cell migration along with HIF-1 alpha accumulation. We observed that non-hypoxic induction of HIP-1 alpha by IL-1 beta in MDAMB231 was associated with increased cell migration, paralleled by upregulation of p38 MAPK phosphorylation and CXCL8/CXCR1 expression. Inhibition of HIF-1 alpha by siRNA resulted in a significant reduction of CXCR1 expression and IL-1 beta-induced cell migration in MDAMB231 cells, thus confirming a role of HIF-1 alpha in the non-hypoxic-IL-1 beta-dependent induction of migratory potentials. Our observation that IL-1 induces HIF-1 alpha 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-1 alpha resulted in the decrease of IL-1 beta-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. (C) 2010 Elsevier Ltd. All rights reserved.
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