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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Mar 24, 2020; 11(3): 121-135
Published online Mar 24, 2020. doi: 10.5306/wjco.v11.i3.121
Roles of cell fusion, hybridization and polyploid cell formation in cancer metastasis
Ivan Shabo, Joar Svanvik, Annelie Lindström, Tanguy Lechertier, Sara Trabulo, James Hulit, Tim Sparey, John Pawelek
Ivan Shabo, Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm SE 171 77, Sweden
Ivan Shabo, Patient Area of Breast Cancer, Sarcoma and Endocrine Tumours, Theme Cancer, Karolinska University Hospital, Stockholm SE 171 76, Sweden
Joar Svanvik, The Transplant Institute, Sahlgrenska University Hospital, Gothenburg SE 413 45, Sweden
Joar Svanvik, Division of Surgery, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping SE 581 83, Sweden
Annelie Lindström, Division of Cell Biology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping SE 581 85, Sweden
Tanguy Lechertier, Sara Trabulo, James Hulit, Tim Sparey, Novintum Bioscience Ltd, London Bioscience Innovation Centre, London NW1 0NH, United Kingdom
John Pawelek, Department of Dermatology and the Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, United States
Author contributions: Shabo I and Svanvik J initiated the review article; Shabo I, Svanvik J, Lindström A, Lechertier T, Trabulo S, Hulit J, Sparey T and Pawelek J contributed to writing and proofreading the paper; Shabo I, Pawelek J and Hulit J designed and edited the figures.
Conflict-of-interest statement: Dr. Tim Spary received salary (not related to the submitted work) from Novintum Bioscience Ltd, London, England. The other authors have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ivan Shabo, MD, PhD, Associate Professor, Surgeon, Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm Nobels väg 6, Stockholm SE 171 77, Sweden. ivan.shabo@ki.se
Received: September 20, 2019
Peer-review started: September 20, 2019
First decision: December 6, 2019
Revised: January 2, 2020
Accepted: March 1, 2020
Article in press: March 1, 2020
Published online: March 24, 2020
Processing time: 178 Days and 9.5 Hours
Abstract

Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation, repair and regeneration. Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations. Factors that stimulate cell fusion are inflammation and hypoxia. Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes, e.g., reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition. There is now considerable in vitro, in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis. Of the many changes in cancer cells after hybridizing with leucocytes, it is notable that hybrids acquire resistance to chemo- and radiation therapy. One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization. Regardless of the mechanism of polyploid cell formation, it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive. Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis. In addition, we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.

Keywords: Cell fusion; Hybrid formation; Polyploidization; Macrophage; Cancer progression; Oncologic treatment resistance

Core tip: Cell fusion is a normal biological process involved in organ formation and tissue repair. Through cell fusion, somatic cells undergo nuclear reprogramming and epigenetic modifications to form hybrid cells with new properties. Fusion of cancer cells with macrophages plays a major role in cancer metastasis and results in resistance to chemo- and radiation therapy. Cell fusion might be a potential target for the development of new antitumor therapies through macrophage depletion in tumour stroma and prevention of cell fusion and post-hybridization events involving chemotaxis and cell migration to lymph nodes and distant metastases.