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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
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.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
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. 8, article id 1994Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 8, article id 1994
Keyword [en]
chemokines; cytokines; mammary gland; microdialysis; microenvironment
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-144847DOI: 10.3389/fimmu.2017.01994ISI: 000422681400002PubMedID: 29387062Scopus ID: 2-s2.0-85040818177OAI: oai:DiVA.org:liu-144847DiVA: diva2:1180128
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2018-02-13Bibliographically approved

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Abrahamsson, AnnelieRzepecka, AnnaDabrosin, Charlotta
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of OncologyDepartment of Medical and Health SciencesDepartment of Radiology in Linköping
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Frontiers in Immunology
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