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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction

Authors: Ivan Shabo, Kristine Midtbö, Henrik Andersson, Emma Åkerlund, Hans Olsson, Pia Wegman, Cecilia Gunnarsson, Annelie Lindström

Published in: BMC Cancer | Issue 1/2015

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Abstract

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 >25 % 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.
Literature
1.
Pawelek JM, Chakraborty AK. Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer. 2008;8(5):377–86.CrossRefPubMed
2.
Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nat. 2002;416(6880):542–5.CrossRef
3.
Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nat. 2010;465(7299):704–12.CrossRef
4.
Pavlath GK, Blau HM. Expression of muscle genes in heterokaryons depends on gene dosage. J Cell Biol. 1986;102(1):124–30.CrossRefPubMed
5.
Rachkovsky M, Sodi S, Chakraborty A, Avissar Y, Bolognia J, McNiff JM, et al. Melanoma x macrophage hybrids with enhanced metastatic potential. Clin Exp Metastasis. 1998;16(4):299–312.CrossRefPubMed
6.
Busund LT, Killie MK, Bartnes K, Seljelid R. Spontaneously formed tumorigenic hybrids of Meth A sarcoma and macrophages grow faster and are better vascularized than the parental tumor. Int J Cancer. 2002;100(4):407–13.CrossRefPubMed
7.
Powell AE, Anderson EC, Davies PS, Silk AD, Pelz C, Impey S, et al. Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming. Cancer Res. 2011;71(4):1497–505.CrossRefPubMedPubMedCentral
8.
Silk AD, Gast CE, Davies PS, Fakhari FD, Vanderbeek GE, Mori M, et al. Fusion between hematopoietic and epithelial cells in adult human intestine. PLoS One. 2013;8(1), e55572.CrossRefPubMedPubMedCentral
9.
10.
Shabo I, Olsson H, Sun XF, Svanvik J. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer. 2009.
11.
Shabo I, Stal O, Olsson H, Dore S, Svanvik J. Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer. 2008;123(4):780–6.CrossRefPubMed
12.
Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64(19):7022–9.CrossRefPubMed
13.
Mallepell S, Krust A, Chambon P, Brisken C. Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A. 2006;103(7):2196–201.CrossRefPubMedPubMedCentral
14.
Shabo I, Olsson H, Stal O, Svanvik J. Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival. Clin Breast Cancer. 2013;13(5):371–7.CrossRefPubMed
15.
Group SBCC. Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. Swedish Breast Cancer Cooperative Group. J Natl Cancer Inst. 1996;88(21):1543–9.CrossRef
16.
Bjerregaard B, Holck S, Christensen IJ, Larsson LI. Syncytin is involved in breast cancer-endothelial cell fusions. Cell Mol Life Sci. 2006;63(16):1906–11.CrossRefPubMed
17.
Busund LT, Killie MK, Bartnes K, Seljelid R. Spontaneously formed tumorigenic hybrids of Meth A sarcoma cells and macrophages in vivo. Int J Cancer. 2003;106(2):153–9.CrossRefPubMed
18.
Maniecki MB, Etzerodt A, Ulhoi BP, Steiniche T, Borre M, Dyrskjot L, et al. Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells. Int J Cancer. 2012;131(10):2320–31.CrossRefPubMed
19.
Hendrix A, Hume AN. Exosome signaling in mammary gland development and cancer. Int J Dev Biol. 2011;55(7-9):879–87.CrossRefPubMed
20.
Tyan S-W, Kuo W-H, Huang C-K, Pan C-C, Shew J-Y, Chang K-J, et al. Breast Cancer Cells Induce Cancer-Associated Fibroblasts to Secrete Hepatocyte Growth Factor to Enhance Breast Tumorigenesis. PLoS One. 2011;6(1):e15313.CrossRefPubMedPubMedCentral
21.
Hagemann T, Wilson J, Kulbe H, Li NF, Leinster DA, Charles K, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol. 2005;175(2):1197–205.CrossRefPubMed
22.
Yang M, Chen J, Su F, Yu B, Su F, Lin L, et al. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10:117.CrossRefPubMedPubMedCentral
23.
Paululat A, Holz A, Renkawitz-Pohl R. Essential genes for myoblast fusion in Drosophila embryogenesis. Mech Dev. 1999;83(1-2):17–26.CrossRefPubMed
24.
Zhou X, Platt JL. Molecular and cellular mechanisms of mammalian cell fusion. Adv Exp Med Biol. 2011;713:33–64.CrossRefPubMed
25.
DeVita Jr VT, Young RC, Canellos GP. Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer. Cancer. 1975;35(1):98–110.CrossRefPubMed
26.
Del Monte U. Does the cell number 10(9) still really fit one gram of tumor tissue? Cell cycle (Georgetown, Tex). 2009;8(3):505–6.CrossRef
27.
Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–7.CrossRefPubMed
28.
Miller FR, McInerney D, Rogers C, Miller BE. Spontaneous fusion between metastatic mammary tumor subpopulations. J Cell Biochem. 1988;36(2):129–36.CrossRefPubMed
29.
Broyles RH, Roth AC, Todd M, Belegu V. Nuclear reprogramming by cell fusion. Methods Mol Biol. 2006;325:47–57.PubMed
30.
Beerenwinkel N, Antal T, Dingli D, Traulsen A, Kinzler KW, Velculescu VE, et al. Genetic progression and the waiting time to cancer. PLoS Comput Biol. 2007;3(11):e225.CrossRefPubMedPubMedCentral
31.
Tada M, Tada T. Epigenetic reprogramming of somatic genomes by electrofusion with embryonic stem cells. Methods Mol Biol. 2006;325:67–79.PubMed
Metadata
Title
Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction
Authors
Ivan Shabo
Kristine Midtbö
Henrik Andersson
Emma Åkerlund
Hans Olsson
Pia Wegman
Cecilia Gunnarsson
Annelie Lindström
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1935-0

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