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Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. (Charlotta Dabrosin)
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. (Charlotta Dabrosin)
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, p. 1-17, article id 1767Article in journal (Refereed) Published
Abstract [en]

Fat is a major tissue component in human breast cancer (BC). Whether breast adipocytes (BAd) affect early stages of BC metastasis is yet unknown. BC progression is dependent on angiogenesis and inflammation, and interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) are key regulators of these events. Here, we show that BAd increased the dissemination of estrogen receptor positive BC cells (BCC) in vivo in the zebrafish model of metastasis, while dissemination of the more aggressive and metastatic BCC such as estrogen receptor negative was unaffected. While anti-VEGF and anti-IL-8 exhibited equal inhibition of angiogenesis at the primary tumor site, anti-IL-8 reduced BCC dissemination whereas anti-VEGF had minor effects on this early metastatic event. Mechanistically, overexpression of cell-adhesion molecules in BCC and neutrophils via IL-8 increased the dissemination of BCC. Importantly, the extracellular in vivo levels of IL-8 were 40-fold higher than those of VEGF in human BC. Our results suggest that IL-8 is a clinical relevant and promising therapeutic target for human BC.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 9, p. 1-17, article id 1767
Keywords [en]
breast cancer, microdialysis, zebrafish, angiogenesis, inflammation
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-150059DOI: 10.3389/fimmu.2018.01767ISI: 000440193400002OAI: oai:DiVA.org:liu-150059DiVA, id: diva2:1237426
Funder
Swedish Cancer Society, 2015/309Swedish Research Council, 2013-2457Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-30

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Publisher's full texthttps://www.frontiersin.org/articles/10.3389/fimmu.2018.01767/full#h11

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Vazquez Rodriguez, GabrielaAbrahamsson, AnnelieJensen, Lasse DDabrosin, Charlotta
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of OncologyDivision of Cardiovascular MedicineDepartment of Clinical Pharmacology
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