title: The role of intratumoral and systemic IL-6 in breast cancer.
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.
authors.affiliation: Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshospitalet, 7641, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Dethlefsen
authors.forename: Grith
authors.initials: G
authors.lastname: Højfeldt
authors.forename: Pernille
authors.initials: P
authors.lastname: Hojman
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D011960:Receptors, Estrogen / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human