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Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. (Charlotta Dabrosin)
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. (Charlotta Dabrosin)
Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
2018 (engelsk)Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, s. 1-17, artikkel-id 1767Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2018. Vol. 9, s. 1-17, artikkel-id 1767
Emneord [en]
breast cancer, microdialysis, zebrafish, angiogenesis, inflammation
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-150059DOI: 10.3389/fimmu.2018.01767ISI: 000440193400002OAI: oai:DiVA.org:liu-150059DiVA, id: diva2:1237426
Forskningsfinansiär
Swedish Cancer Society, 2015/309Swedish Research Council, 2013-2457Tilgjengelig fra: 2018-08-08 Laget: 2018-08-08 Sist oppdatert: 2018-08-30

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