Abstract
Estrogen-receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that interleukin-8 (IL-8) was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells, and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of IL-8, but not with IL-8 receptor levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by two fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness.
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Acknowledgements
We thank Dr T Maudelonde for a critical reading of the manuscript and Professor J P Daures for statistical analysis. We thank the Vector Core of the University Hospital of Nantes supported by the Association Francaise contre les Myopathies (AFM) for the production of Adenoviruses. This work was supported by grants from ARC (Association pour la Recherche contre le Cancer, Grant No. 4302), la Ligue Nationale contre le Cancer (Comite du Gard), INSERM and CNRS.
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Freund, A., Chauveau, C., Brouillet, JP. et al. IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells. Oncogene 22, 256–265 (2003). https://doi.org/10.1038/sj.onc.1206113
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DOI: https://doi.org/10.1038/sj.onc.1206113
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