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Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer
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.
Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
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. 8, artikkel-id 1994Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2018. Vol. 8, artikkel-id 1994
Emneord [en]
chemokines; cytokines; mammary gland; microdialysis; microenvironment
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-144847DOI: 10.3389/fimmu.2017.01994ISI: 000422681400002PubMedID: 29387062Scopus ID: 2-s2.0-85040818177OAI: oai:DiVA.org:liu-144847DiVA, id: diva2:1180128
Tilgjengelig fra: 2018-02-05 Laget: 2018-02-05 Sist oppdatert: 2018-02-21bibliografisk kontrollert

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