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The role of intratumoral and systemic IL-6 in breast cancer

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Abstract

Chronic low-grade inflammation plays an important role in the pathogenesis of several cancer forms including breast cancer. The pleiotropic cytokine IL-6 is a key player in systemic inflammation, regulating both the inflammatory response and tissue metabolism during acute stimulations. Here, we review the associations between IL-6 and breast cancer ranging from in vitro cell culture studies to clinical studies, covering the role of IL-6 in controlling breast cancer cell growth, regulation of cancer stem cell renewal, as well as breast cancer cell migration. Moreover, associations between circulating IL-6 and risk of breast cancer, prognosis for patients with prevalent disease, adverse effects and interventions to control systemic IL-6 levels in patients are discussed. In summary, direct application of IL-6 on breast cancer cells inhibits proliferation in estrogen receptor positive cells, while high circulating IL-6 levels are correlated with a poor prognosis in breast cancer patients. This discrepancy reflects distinct roles of IL-6, with elevated systemic levels being a biomarker for tumor burden, physical inactivity, and impaired metabolism, while local intratumoral IL-6 signaling is important for controlling breast cancer cell growth, metastasis, and self renewal of cancer stem cells.

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Acknowledgments

The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (# 02-512-55). This study was further supported by the Danish Medical Research Council, and Rigshospitalets Research Funds. CIM is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology and Innovation.

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  1. Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshospitalet, 7641, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Christine Dethlefsen, Grith Højfeldt & Pernille Hojman

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  1. Christine Dethlefsen
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  2. Grith Højfeldt
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Correspondence to Pernille Hojman.

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Christine Dethlefsen and Grith Højfeldt contributed equally to the study.

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Dethlefsen, C., Højfeldt, G. & Hojman, P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res Treat 138, 657–664 (2013). https://doi.org/10.1007/s10549-013-2488-z

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