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Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
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2015 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, no 1, 922- p.Article in journal (Refereed) Published
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Abstract [en]

Background: Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor stroma. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast. Methods: Monocytes, harvested from male blood donor, were activated to M2 macrophages and co-cultured in ThinCert transwell system with GFP-labeled MCF-7 cancer cells. MCF7/macrophage hybrids were generated by spontaneous cell fusion, isolated by fluorescence-activated cell sorting and confirmed by fluorescence microscopy, short tandem repeats analysis and flow cytometry. CD163 expression was evaluated in breast tumor samples material from 127 women by immunohistochemistry. Results: MCF-7/macrophage hybrids were generated spontaneously at average rate of 2 % and showed phenotypic and genetic traits from both maternal cells. CD163 expression in MCF-7 cells could not be induced by paracrine interaction with M2-activated macrophages. CD163 positive cancer cells in tumor sections grew in clonal collection and a cutoff point greater than25 % of positive cancer cells was significantly correlated to disease free and overall survival. Conclusions: In conclusion, macrophage traits in breast cancer might be caused by cell fusion rather than explained by paracrine cellular interaction. These data provide new insights into the role of cell fusion in breast cancer and contributes to the development of clinical markers to identify cell fusion.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD , 2015. Vol. 15, no 1, 922- p.
Keyword [en]
Cell fusion; Macrophages; Paracrine cellular interaction; Tumor markers
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-123328DOI: 10.1186/s12885-015-1935-0ISI: 000365276000001PubMedID: 26585897OAI: oai:DiVA.org:liu-123328DiVA: diva2:882202
Note

Funding Agencies|County Council of Ostergotland (Sweden); National Organization of Breast Cancer Associations (Sweden); Bengt Ihre Foundation (Swedish Surgical Society)

Available from: 2015-12-14 Created: 2015-12-11 Last updated: 2017-12-01

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Shabo, IvanMidtbö, Kristine MariaAndersson, HenrikOlsson, HansGunnarsson, CeciliaLindström, Annelie
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Division of Clinical SciencesDepartment of Surgery in LinköpingFaculty of Medicine and Health SciencesDivision of Cell BiologyDivision of Neuro and Inflammation ScienceDepartment of Clinical Pathology and Clinical GeneticsDepartment of Clinical and Experimental Medicine
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