Abstract
Cell fusion is a cellular mechanism in which cell membranes of two or more cells fuse to become a new hybrid cell. Cell fusion plays an important role in several physiological tasks such as fertilization, organogenesis, inflammatory response, and tissue repair. However, cell fusion aids in the development of a wide range of pathological conditions such as inflammation and cancer. Cell fusion of normal somatic cells is a tightly controlled process that is limited to only a few cell types in humans, resulting in terminally differentiated multinucleated cells incapable of proliferation. However, this tightly controlled process becomes dysregulated due to genetic alterations and leads to the development of cancer. In this review, the implications of cell fusion and its role in carcinogenesis are discussed in detail.
Keywords:
Cell fusion, tumor microenvironment, carcinogenesis
References
1
Benirschke K. Remarkable placenta. Clin Anat. 1998;11(3):194-205.
2
Taylor MV. Muscle differentiation: how two cells become one. Curr Biol. 2002;12(6):R224-228.
3
Eckert DM, Kim PS. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem. July 2001;70:777-810.
4
Calder LJ, Rosenthal PB. Cryomicroscopy provides structural snapshots of influenza virus membrane fusion. Nat Struct Mol Biol. 2016;23(9):853-858.
5
Hernández JM, Podbilewicz B. The hallmarks of cell-cell fusion. Development. 2017;144(24):4481-4495.
6
Brukman NG, Uygur B, Podbilewicz B, Chernomordik LV. How cells fuse. J Cell Biol. 2019;218(5):1436-1451.
7
Wang HF, Xiang W, Xue BZ, et al. Cell fusion in cancer hallmarks: Current research status and future indications. Oncol Lett. 2021;22(1):530.
8
Aichel O. Über zellverschmelzung mit quantitativ abnormer chromosomenverteilung als ursache der geschwulstbildung. In: Roux W, ed. Vorträge und Aufsätze über Entwicklungsmechanik der Organismen. Germany: Wilhelm Engelmann, Leipzig; 1911. p.1-115.
9
Vineis P, Schatzkin A, Potter JD. Models of carcinogenesis: an overview. Carcinogenesis. 2010;31(10):1703-1709.
10
Zhou X, Merchak K, Lee W, Grande JP, Cascalho M, Platt JL. Cell fusion connects oncogenesis with tumor evolution. Am J Pathol. 2015;185(7):2049-2060.
11
Duncan AW, Taylor MH, Hickey RD, et al. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature. 2010;467(7316):707-710.
12
Sottile F, Aulicino F, Theka I, Cosma MP. Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis. Sci Rep. Nov 2016;6:36863.
13
Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009;460(7252):278-282.
14
Weiler J, Dittmar T. Cell fusion in human cancer: the dark matter hypothesis. Cells. 2019;8(2):132.
15
Bertone G. The moment of truth for WIMP dark matter. Nature. 2010;468(7322):389-393.
16
Ross JL. The dark matter of biology. Biophys J. 2016;111(5):909-916.
17
Scarpa A, Mafficini A. Non-coding regulatory variations: the dark matter of pancreatic cancer genomics. Gut. 2018;67(3):399-400.
18
Bolouri H. Network dynamics in the tumor microenvironment. Semin Cancer Biol. Feb 2015;30:52-59.
19
Zhou Z, Lu ZR. Molecular imaging of the tumor microenvironment. Adv Drug Deliv Rev. Apr 2017;113:24-48.
20
Han L, Xu J, Xu Q, Zhang B, Lam EW, Sun Y. Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies. Med Res Rev. 2017;37(6):1318-1349.
21
Kemp K, Wilkins A, Scolding N. Cell fusion in the brain: two cells forward, one cell back. Acta Neuropathol. 2014;128(5):629-638.
22
Yang L, Lin PC. Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression. Semin Cancer Biol. Dec 2017;47:185-195.
23
Weiler J, Mohr M, Zänker KS, Dittmar T. Matrix metalloproteinase-9 (MMP9) is involved in the TNF-α-induced fusion of human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells. Cell Commun Signal. 2018;16(1):14.
24
Powell AE, Anderson EC, Davies PS, et al. Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming. Cancer Res. 2011;71(4):1497-1505.
25
Garvin S, Oda H, Arnesson LG, Lindström A, Shabo I. Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery. J Cancer Res Clin Oncol. 2018;144(7):1253-1263.
26
Lazova R, Chakraborty A, Pawelek JM. Leukocyte-cancer cell fusion: initiator of the warburg effect in malignancy? Adv Exp Med Biol. April 2011;714:151-172.
27
Pawelek JM. Tumour cell hybridization and metastasis revisited. Melanoma Res. 2000;10(6):507-514.
28
De Baetselier P, Roos E, Brys L, et al. Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells. Cancer Metastasis Rev. 1984;3(1):5-24.
29
Munzarová M, Kovarík J. Is cancer a macrophage-mediated autoaggressive disease? Lancet. 1987;1(8539):952-954.
30
Medvinsky A, Smith A. Stem cells: Fusion brings down barriers. Nature. 2003;422(6934):823-825.
31
Koido S. Dendritic-tumor fusion cell-based cancer vaccines. Int J Mol Sci. 2016;17(6):828.
