Abstract
BackgroundCell 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.MethodsMonocytes, 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.ResultsMCF-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 >25 % of positive cancer cells was significantly correlated to disease free and overall survival.ConclusionsIn 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.
Highlights
Cell fusion is a natural process in normal development and tissue regeneration
Based on cell fusion theory and the assumption that the macrophage–cancer cell fusion creates hybrids expressing phenotypic characteristics of macrophages, we reported in previous studies that the macrophage-specific marker, CD163, was expressed in breast and colorectal cancers
Cells that expressed only Green fluorescent protein (GFP) were sorted as MCF-7 cancer cells, and GFP-negative cells were defined as macrophages
Summary
Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast. The hybrids acquire genetic and phenotypic characteristics from both maternal cells [1, 2]. Several reports present evidence that macrophages are an important partner in this process. Fusion between macrophages and cancer cells generates hybrids with increased. Powell et al in an experimental animal model with parabiosis, showed in vivo evidence of fusion between circulating bone-marrowderived cells (BMDCs) and tumor epithelium during tumorigenesis, demonstrating that macrophages were a cellular partner in this process [7]. Circulating hybrids are reported in colorectal and pancreatic cancer patients [9]
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