Cell fusion in tumor development: Accelerated genetic evolution

Critical Reviews in Oncogenesis

Volumn 18, Issue 1-2, 2013, Pages 19-42

  Harkness, Ty ^a   Weaver, Beth A ^b,c   Alexander, Caroline M ^a,c   Ogle, Brenda M ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^c UNIVERSITY OF WISCONSIN   (United States)

Author keywords

Chromosomal instability; Metastasis; Multipolar mitosis; Polyploidy; Reprogramming

Indexed keywords

BETA GALACTOSIDASE; CELL SURFACE PROTEIN; CENTROMERE PROTEIN E; CRE RECOMBINASE; ENVELOPE PROTEIN; GENOMIC DNA; GREEN FLUORESCENT PROTEIN; NAKED DNA; UVOMORULIN; VON WILLEBRAND FACTOR;

ANEUPLOIDY; ARTICLE; BONE MARROW CELL; CANCER CELL; CARCINOGENESIS; CELL FUSION; CELL MATURATION; CELL MEMBRANE; CHROMOSOMAL INSTABILITY; CHROMOSOME SEGREGATION; CLONAL EVOLUTION; CYTOPLASM; DIPLOIDY; DISEASE COURSE; DNA DAMAGE; GAMETE; GENE EXPRESSION; GENE MUTATION; GENE TRANSFER; GENETIC VARIABILITY; HUMAN; HUMAN CHROMOSOME; HUMAN IMMUNODEFICIENCY VIRUS 1; HYBRIDOMA; MACROPHAGE; MEMBRANE FUSION; MESENCHYMAL STEM CELL; METASTASIS; MITOSIS; MUSCLE CELL; MYOBLAST; NONHUMAN; OSTEOCLAST; PHENOTYPE; POLYPLOIDY; PRIMARY TUMOR; PRIORITY JOURNAL; SHORT TANDEM REPEAT; SINGLE NUCLEOTIDE POLYMORPHISM; TETRAPLOIDY; TROPHOBLAST; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; VIRUS CELL INTERACTION; VIRUS INFECTION;

CELL FUSION; CELL TRANSFORMATION, NEOPLASTIC; DNA REPAIR; HUMANS; KARYOTYPING; MITOSIS; MUTATION; NEOPLASM METASTASIS; NEOPLASMS;

EID: 84875345071     PISSN: 08939675     EISSN: 21626448     Source Type: Journal    
DOI: 10.1615/CritRevOncog.v18.i1-2.30     Document Type: Article

References (193)

1. Gao P, Zheng J. High-risk HPV E5-induced cell fusion: a critical initiating event in the early stage of HPV-associated cervical cancer. J Virol. 2010;7:238.
2. Paget S. The distribution of secondary growths in cancer of breast. Lancet. 1889;1:571-3.
3. Huang M, Li Y, Zhang H, Nan F. Research Breast cancer stromal fibroblasts promote the generation of CD44+CD24-cells through SDF-1/CXCR4 interaction. J Exp Clin Cancer Res. 2010;29:80.
4. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141:52-67.
5. Pinto MP, Badtke MM, Dudevoir ML, Harrell JC, Jacobsen BM, Horwitz KB. Vascular Endothelial Growth Factor Secreted by Activated Stroma Enhances Angiogenesis and Hormone-Independent Growth of Estrogen Receptor-Positive Breast Cancer. Cancer Research. 2010;70:2655.
6. Tyan SW, Kuo WH, Huang CK, Pan CC, Shew JY, Chang KJ, Lee, EYHP, Lee WH. Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis. PloS One. 2011;6:e15313.
7. Su G, Blaine SA, Qiao D, Friedl A. Shedding of syndecan-1 by stromal fibroblasts stimulates human breast cancer cell proliferation via FGF2 activation. World J Biol Chem. 2007;282:14906-15.
8. Wu M, Jung L, Cooper AB, Fleet C, Chen L, Breault L, Clark K, Cai Z, Vincent S, Bottega S. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice. Proceedings of the National Academy of Sciences. 2009;106:7022.
9. Trimis G, Chatzistamou I, Politi K, Kiaris H, Papavassiliou AG. Expression of p21waf1/Cip1 in stromal fibroblasts of primary breast tumors. Hum Mol Genet. 2008;17:3,596-600.
10. Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A. Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Research. 2005;65:1,627-30.
11. Apostolopoulou M, Ligon L. Cadherin-23 Mediates Heterotypic Cell-Cell Adhesion between Breast Cancer Epithelial Cells and Fibroblasts. PloS One. 2012;7:e33289.
12. Forkner CE. The Origin and Fate of Two Types of Multi-nucleated Giant Cells in the Circulating Blood. J Exp Med. 1930;52:279.
13. Duelli D, Lazebnik Y. Cell fusion: a hidden enemy? Cancer Cell. 2003;3:445-8.
14. Ogle BM, Cascalho M, Platt JL. Biological implications of cell fusion. Nat Rev Mol Cell Biol. 2005;6:567-75.
15. Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan Y, Lidov HG, Bonnemann CG. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J Clin Invest. 2002;110:807-14.
16. Gibson AJ, Karasinski J, Relvas J, Moss J, Sherratt TG, Strong PN, Watt DJ. Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle. J Cell Sci. 1995;108(Pt 1):207-14.
17. Weimann JM, Johansson CB, Trejo A, Blau HM. Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nat Cell Biol. 2003;5:959-66.
18. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 2003;425:968-73.
19. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 2003;422:897-901.
20. Yilmaz Y, Lazova R, Qumsiyeh M, Cooper D, Pawelek J. Donor Y chromosome in renal carcinoma cells of a female BMT recipient: visualization of putative BMT-tumor hybrids by FISH. Bone Marrow Transplant. 2005;35:1021-4.
21. Hyman E, Kauraniemi P, Hautaniemi S, Wolf M, Mousses S, Rozenblum E, Ringnér M, Sauter G, Monni O, Elkahloun A. Impact of DNA amplification on gene expression patterns in breast cancer. Cancer Research. 2002;62:6240.
22. Pollack JR, Sørlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE, Tibshirani R, Botstein D, Børresen-Dale AL, Brown PO. Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proceedings of the National Academy of Sciences. 2002;99:12963.
23. Hau PM, Siu WY, Wong N, Lai PB, Poon RY. Polyploidization increases the sensitivity to DNA-damaging agents in mammalian cells. FEBS Lett. 2006;580:4727-36.
24. Wong C, Stearns T. Mammalian cells lack checkpoints for tetraploidy, aberrant centrosome number, and cytokinesis failure. BMC Cell Biol. 2005;6:6.
25. Gao P, Zheng J. Oncogenic virus-mediated cell fusion: new insights into initiation and progression of oncogenic viruses--related cancers. Cancer Lett. 2011;303:1-8.
26. Duelli D, Lazebnik Y. Cell-to-cell fusion as a link between viruses and cancer. Nat Rev Cancer. 2007;7:968-76.
27. Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009;460:278-82.
28. Yang Z, Lončarek J, Khodjakov A, Rieder CL. Extra centrosomes and/or chromosomes prolong mitosis in human cells. Nat Cell Biol. 2008;10:748-51.
29. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495-7.
30. Olsson L, Kronstrom H, Cambon-De Mouzon A, Honzik C, Brodin T, Jakobsen B. Antibody producing human-human hybridomas. I. Technical aspects. J Immunoll Methods. 1983;61:17-32.
31. Ebeling SB, Bos HMK, Slater R, Overkamp WJI, Cuthbert AP, Newbold RF, Zdzienicka MZ, Aarden LA. Human chromosome 21 determines growth factor dependence in human/mouse B-cell hybridomas. Cancer Research. 1998;58:2863-8.
32. Dalm MCF, Jansen M, Keijzer TMP, van Grunsven WMJ, Oudshoorn A, Tramper J, Martens DE. Stable hybridoma cultivation in a pilot-scale acoustic perfusion system: Long-term process performance and effect of recirculation rate. Biotechnology and Bioengineering. 2005;91:894-900.
33. Dewar V, Voet P, Denamur F, Smal J. Industrial implementation of in vitro production of monoclonal antibodies. ILAR J. 2005;46:307.
34. Mable BK, Otto SP. Masking and purging mutations following EMS treatment in haploid, diploid and tetraploid yeast (Saccharomyces cerevisiae). Genetical Research. 2001;77:9-26.
35. Levine DS, Sanchez CA, Rabinovitch PS, Reid BJ. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer. Proceedings of the National Academy of Sciences. 1991;88:6427.
36. Nigg EA. Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer. 2002;2:815-25.
37. Vitale I, Senovilla L, Jemaà M, Michaud M, Galluzzi L, Kepp O, Nanty L, Criollo A, Rello-Varona S, Manic G. Multipolar mitosis of tetraploid cells: inhibition by p. 53 and dependency on Mos. EMBO J. 2010;29:1272-84.
38. Grompe M. The role of bone marrow stem cells in liver regeneration. Semin Liver Dis. 2003;23:363-72.
39. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature. 2003;422:901-4.
40. Duncan AW, Hickey RD, Paulk NK, Culberson AJ, Olson SB, Finegold MJ, Grompe M. Ploidy reductions in murine fusion-derived hepatocytes. PLoS Genet. 2009;5:e1000385.
41. Duncan AW, Taylor MH, Hickey RD, Newell AEH, Lenzi ML, Olson SB, Finegold MJ, Grompe M. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature. 2010;467:707-10.
42. Gupta S. Hepatic polyploidy and liver growth control. Semin Cancer Biol. 2000;10:161-71.
43. Oberringer M, Lothschütz D, Jennewein M, Koschnick M, Mutschler W, Hanselmann RG. Centrosome multiplication accompanies a transient clustering of polyploid cells during tissue repair. Mol Cell Biol Res Comm. 1999;2:190-6.
44. Storchova Z, Pellman D. From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol. 2004;5:45-54.
45. Gurdon J, Melton D. Nuclear reprogramming in cells. Science. 2008;322:1811.
46. Lin HP, Ogle BM. Nuclear Reprogramming. Encyclopedia for Stem Cell Research. CA: Sage Publications; 2008. 369-99.
47. Wilmut I, Schnieke A, McWhir J, Kind A, Campbell K. Viable offspring derived from fetal and adult mammalian cells. Clones and Clones: Facts and Fantasies about Human Cloning. 1999:21.
48. Blau HM, Chiu CP, Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983;32:1171-80.
49. Davidson RL, Ephrussi B, Yamamoto K. Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization. Proceedings of the National Academy of Sciences of the United States of America. 1966;56:1437.
50. Tada M, Tada T, Lefebvre L, Barton SC, Surani MA. Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J. 1997;16:6510-20.
51. Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nature. 2010;465:704-12.
52. Kimura H, Tada M, Nakatsuji N, Tada T. Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol. 2004;24:5710.
53. Powell AE, Anderson EC, Davies PS, Silk AD, Pelz C, Impey S, Wong MH. Fusion between intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming. Cancer Research. 2011;71:1497.
54. Wolfe KH. Yesterday's polyploids and the mystery of diploidization. Nature Reviews Genetics. 2001;2:333-41.
55. Wendel JF. Genome evolution in polyploids. Plant Mol Biol. 2000;42:225-49.
56. Chester M, Gallagher JP, Symonds VV, da Silva AVC, Mavrodiev EV, Leitch AR, Soltis PS, Soltis DE. Extensive chromosomal variation in a recently formed natural allopolyploid species, Tragopogon miscellus (Asteraceae). Proceedings of the National Academy of Sciences. 2012;109:1176-81.
57. Eldredge N, Gould SJ. Punctuated equilibria: an alternative to phyletic gradualism. Models in Paleobiology. 1972;82:115.
58. Sagan L. On the origin of mitosing cells. J Theor Biol. 1967;14:225-74, IN1-IN6.
59. Oren-Suissa M, Podbilewicz B. Cell fusion during development. Trends Cell Biol. 2007;17:537-46.
60. Chen EH, Grote E, Mohler W, Vignery A. Cell-cell fusion. FEBS Lett. 2007;581:2181-93.
61. Helming L, Gordon S. Molecular mediators of macrophage fusion. Trends Cell Biol. 2009;19:514-22.
62. Shinn-Thomas JH, Mohler WA. Chapter five-New Insights into the Mechanisms and Roles of Cell-Cell Fusion. In: Kwang WJ, editor. Int Rev Cell Mol Biol: Academic Press; 2011. p.149-209.
63. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337-42.
64. Moreno JL, Mikhailenko I, Tondravi MM, Keegan AD. IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin. J Leukoc Biol. 2007;82:1542-53.
65. Yagi M, Ninomiya K, Fujita N, Suzuki T, Iwasaki R, Morita K, Hosogane N, Matsuo K, Toyama Y, Suda T. Induction of DC-STAMP by Alternative Activation and Downstream Signaling Mechanisms. J Bone Miner Res. 2007;22:992-1,001.
66. Yagi M, Miyamoto T, Sawatani Y, Iwamoto K, Hosogane N, Fujita N, Morita K, Ninomiya K, Suzuki T, Miyamoto K. DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. Journal Exp Med. 2005;202:345.
67. Helming L, Tomasello E, Kyriakides TR, Martinez FO, Takai T, Gordon S, Vivier E. Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Sci Signal. 2008;1:ra11.
68. Kyriakides TR, Foster MJ, Keeney GE, Tsai A, Giachelli CM, Clark-Lewis I, Rollins BJ, Bornstein P. The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation. The American Journal of Pathology. 2004;165:2157.
69. Vignery A. Macrophage fusion: the making of osteoclasts and giant cells. J Exp Med. 2005;202:337-40.
70. Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138:286-99.
71. Liu AY. Differential expression of cell surface molecules in prostate cancer cells. Cancer Research. 2000;60:3429.
72. Baier P, Eggstein S, Wolff-Vorbeck G, Baumgartner U, Hopt U. Chemokines in human colorectal carcinoma. Anticancer Research. 2005;25:3581.
73. Zijlmans HJ, Fleuren G, Baelde H, Eilers PHC, Kenter G, Gorter A. The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11. 2. Journal Pathol. 2006;208:507-17.
74. Pawelek JM, Chakraborty AK. The cancer cell-leukocyte fusion theory of metastasis. Adv Cancer Res. 2008;101:397-444.
75. Aspord C, Pedroza-Gonzalez A, Gallegos M, Tindle S, Burton EC, Su D, Marches F, Banchereau J, Palucka AK. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med. 2007;204:1037.
76. Sens KL, Zhang S, Jin P, Duan R, Zhang G, Luo F, Parachini L, Chen EH. An invasive podosome-like structure promotes fusion pore formation during myoblast fusion. J Cell Biol. 2010;191:1013.
77. Jay SM, Skokos E, Laiwalla F, Krady MM, Kyriakides TR. Foreign body giant cell formation is preceded by lamellipodia formation and can be attenuated by inhibition of Rac1 activation. Am J Pathol. 2007;171:632.
78. Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, Suzuki K, Kosai K, Inoue K, Ogura A. Requirement of CD9 on the egg plasma membrane for fertilization. Science. 2000;287:321.
79. Kaji K, Oda S, Miyazaki S, Kudo A. Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm-egg fusion. Developmental Biology. 2002;247:327-34.
80. Jégou A, Ziyyat A, Barraud-Lange V, Perez E, Wolf JP, Pincet F, Gourier C. CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization. Proceedings of the National Academy of Sciences. 2011;108:10,946.
81. Okabe M, Adachi T, Takada K, Oda H, Yagasaki M, Kohama Y, Mimura T. Capacitation-related changes in antigen distribution on mouse sperm heads and its relation to fertilization rate in vitro. J Reprod Immunol. 1987;11:91-100.
82. Inoue N, Ikawa M, Isotani A, Okabe M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature. 2005;434:234-8.
83. Larsson LI, Bjerregaard B, Talts JF. Cell fusions in mammals. Histochem Cell Biol. 2008;129:551-61.
84. Chen EH, Olson EN. Unveiling the mechanisms of cell-cell fusion. Science. 2005;308:369.
85. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495-7.
86. Hu L, Plafker K, Vorozhko V, Zuna RE, Hanigan MH, Gorbsky GJ, Plafker SM, Angeletti PC, Ceresa BP. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion. Virology. 2009;384:125-34.
87. Iessi E, Marino ML, Lozupone F, Fais S, De Milito A. Tumor acidity and malignancy: novel aspects in the design of anti-tumor therapy. Cancer Therapy. 2008;6:55-66.
88. Storchova Z, Kuffer C. The consequences of tetraploidy and aneuploidy. J Cell Sci. 2008;121:3,859.
89. Hansemann D. Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Virchows Archiv. 1890;119:299-326.
90. Storchová Z, Breneman A, Cande J, Dunn J, Burbank K, O'Toole E, Pellman D. Genome-wide genetic analysis of polyploidy in yeast. Nature. 2006;443:541-7.
91. Lu X, Kang Y. Cell fusion as a hidden force in tumor progression. Cancer Research. 2009;69:8,536.
92. Rajagopalan H, Lengauer C. Aneuploidy and cancer. Nature. 2004;432:338-41.
93. Barrett MT, Pritchard D, Palanca-Wessels C, Anderson J, Reid BJ, Rabinovitch PS. Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett's esophagus. Cancer Research. 2003;63:4,211.
94. Rabinovitch PS, Longton G, Blount PL, Levine DS, Reid BJ. Predictors of progression in Barrett's esophagus III: baseline flow cytometric variables. Am J Gastroenterol. 2001;96:3071-83.
95. Olaharski AJ, Sotelo R, Solorza-Luna G, Gonsebatt ME, Guzman P, Mohar A, Eastmond DA. Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. Carcinogenesis. 2006;27:337-43.
96. Abou-Elhamd KEA, Habib TN. The flow cytometric analysis of premalignant and malignant lesions in head and neck squamous cell carcinoma. Oral Oncol. 2007;43:366-72.
97. Dictor M, Fernö M, Baldetorp B. Flow cytometric DNA content in Kaposi's sarcoma by histologic stage. Comparison with Angiosarcoma. Analytical and Quantitative Cytology and Histology/the International Academy of Cytology [and] American Society of Cytology. 1991;13:201.
98. Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005;437:1043-7.
99. Roschke AV, Tonon G, Gehlhaus KS, McTyre N, Bussey KJ, Lababidi S, Scudiero DA, Weinstein JN, Kirsch IR. Karyotypic complexity of the NCI-60 drug-screening panel. Cancer Research. 2003;63:8,634.
100. Abdel-Rahman WM, Katsura K, Rens W, Gorman PA, Sheer D, Bicknell D, Bodmer WF, Arends MJ, Wyllie AH, Edwards PAW. Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement. Proceedings of the National Academy of Sciences. 2001;98:2,538.
101. Sirivatanauksorn V, Sirivatanauksorn Y, Gorman PA, Davidson JM, Sheer D, Moore PS, Scarpa A, Edwards PAW, Lemoine NR. Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping. Int J Cancer. 2001;91:350-8.
102. Davidson J, Gorringe K, Chin S, Orsetti B, Besret C, Courtay-Cahen C, Roberts I, Theillet C, Caldas C, Edwards P. Molecular cytogenetic analysis of breast cancer cell lines. Br J Cancer. 2000;83:1,309.
103. Wistuba II, Bryant D, Behrens C, Milchgrub S, Virmani AK, Ashfaq R, Minna JD, Gazdar AF. Comparison of features of human lung cancer cell lines and their corresponding tumors. ClinCancer Res. 1999;5:991-1,000.
104. Andreassen PR, Lohez OD, Lacroix FB, Margolis RL. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell. 2001;12:1,315-28.
105. Margolis RL, Lohez OD, Andreassen PR. G1 tetraploidy checkpoint and the suppression of tumorigenesis. J Cell Biochem. 2003;88:673-83.
106. Uetake Y, Sluder G. Cell cycle progression after cleavage failure. J Cell Biol. 2004;165:609.
107. Duelli DM, Hearn S, Myers MP, Lazebnik Y. A primate virus generates transformed human cells by fusion. J Cell Biol. 2005;171:493-503.
108. Duelli DM, Padilla-Nash HM, Berman D, Murphy KM, Ried T, Lazebnik Y. A virus causes cancer by inducing massive chromosomal instability through cell fusion. Curr Biol: CB. 2007;17:431-7.
109. Greenberg R. Telomeres, crisis and cancer. CurrMol Med. 2005;5:213-8.
110. Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG, Kuo WL, Ljung BM, Chew K, Myambo K. In situ analyses of genome instability in breast cancer. Nat Genet. 2004;36:984-8.
111. Lin TT, Letsolo BT, Jones RE, Rowson J, Pratt G, Hewamana S, Fegan C, Pepper C, Baird DM. Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis. Blood. 2010;116:1,899-907.
112. Stewénius Y, Gorunova L, Jonson T, Larsson N, Höglund M, Mandahl N, Mertens F, Mitelman F, Gisselsson D. Structural and numerical chromosome changes in colon cancer develop through telomere-mediated anaphase bridges, not through mitotic multipolarity. Proceedings of the National Academy of Sciences of the United States of America. 2005;102:5,541.
113. Chan JY. A Clinical Overview of Centrosome Amplification in Human Cancers. Int J Biol Sci. 2011;7:1,122.
114. Weaver BAA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW. Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2007;11:25-36.
115. Rao CV, Yang YM, Swamy MV, Liu T, Fang Y, Mahmood R, Jhanwar-Uniyal M, Dai W. Colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice is linked to premature separation of sister chromatids and enhanced genomic instability. Proceedings of the National Academy of Sciences of the United States of America. 2005;102:4,365.
116. Sussan TE, Annan Yang FL, Ostrowski MC, Reeves RH. Trisomy represses ApcMin-mediated tumours in mouse models of Down's syndrome. Nature. 2008;451:73-5.
117. Jeganathan K, Malureanu L, Baker DJ, Abraham SC, Van Deursen JM. Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. J Cell Biol. 2007;179:255-67.
118. Wang Z, Yu R, Melmed S. Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division. Mol Endocrinol. 2001;15:1,870-9.
119. Yu R, Lu W, Chen J, McCabe CJ, Melmed S. Overexpressed pituitary tumor-transforming gene causes aneuploidy in live human cells. Endocrinology. 2003;144:4,991-8.
120. Chesnokova V, Kovacs K, Castro AV, Zonis S, Melmed S. Pituitary hypoplasia in Pttg-/-mice is protective for Rb+/-pituitary tumorigenesis. Mol Endocrinol. 2005;19:2,371-9.
121. Donangelo I, Gutman S, Horvath E, Kovacs K, Wawrowsky K, Mount M, Melmed S. Pituitary tumor transforming gene overexpression facilitates pituitary tumor development. Endocrinology. 2006;147:4,781-91.
122. Yang Q, Rasmussen SA, Friedman J. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002;359:1,019-25.
123. Satge D, Sommelet D, Geneix A, Nishi M, Malet P, Vekemans M. A tumor profile in Down syndrome. Am J Med Genet. 1998;78:207-16.
124. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet. 2000;355:165-9.
125. Stanbridge EJ. Suppression of malignancy in human cells. Nature. 1976;260:17.
126. Harris H, Miller O, Klein G, Worst P, Tachibana T. Suppression of malignancy by cell fusion. Nature. 1969;223:363.
127. Anderson M, Stanbridge E. Tumor suppressor genes studied by cell hybridization and chromosome transfer. FASEB J. 1993;7:826.
128. Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations and gene fusions in cancer. 2011.
129. Kuukasjärvi T, Karhu R, Tanner M, Kähkönen M, Schäffer A, Nupponen N, Pennanen S, Kallioniemi A, Kallioniemi OP, Isola J. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Research. 1997;57:1,597-604.
130. Waldman FM, DeVries S, Chew KL, Moore II DH, Kerlikowske K, Ljung BM. Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences. J Nat Cancer Inst. 2000;92:313-20.
131. Hunter KW, Crawford N, Alsarraj J. Mechanisms of metastasis. Breast Cancer Res. 2008;10:S2.
132. Lazebnik Y. What are the hallmarks of cancer? Nature Reviews Cancer. 2010;10:232-3.
133. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-74.
134. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer. 2009;9:302-12.
135. Katoh M, Neumaier M, Nezam R, Izbicki J, Schumacher U. Correlation of circulating tumor cells with tumor size and metastatic load in a spontaneous lung metastasis model. Anticancer Research. 2004;24:1,421-6.
136. Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010;464:999-1,005.
137. Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J ClinOncol. 1994;12:1,272-80.
138. Van de Wouw A, Janssen-Heijnen M, Coebergh J, Hillen H. Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984-1992. Eur J Cancer. 2002;38:409-13.
139. Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol. 1997;65:284-97.
140. Peer PGM, Van Dijck JAAM, Verbeek ALM, Hendriks JHCL, Holland R. Age-dependent growth rate of primary breast cancer. Cancer. 1993;71:3,547-51.
141. Parris GE. Clinically significant cancer evolves from transient mutated and/or aneuploid neoplasia by cell fusion to form unstable syncytia that give rise to ecologically viable parasite species. Med Hypotheses. 2005;65:846-50.
142. Duesberg P, Fabarius A, Hehlmann R. Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells. IUBMB Life. 2004;56(2):65-81.
143. Muller H. The relation of recombination to mutational advance. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1964;1:2-9.
144. Risques RA, Moreno V, Ribas M, Marcuello E, Capellà G, Peinado MA. Genetic pathways and genome-wide determinants of clinical outcome in colorectal cancer. Cancer Research. 2003;63:7,206.
145. Staibano S, Franco R, Mezza E, Chieffi P, Sinisi A, Pasquali D, Errico M, Nappi C, Tremolaterra F, Somma P. Loss of oestrogen receptor β, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours. Histopathology. 2003;43:254-62.
146. Choma D, Daures J, Quantin X, Pujol J. Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data. Br J Cancer. 2001;85:14.
147. Outhern JF, Warshaw AL, Lewandrowski KB. DNA ploidy analysis of mucinous cystic tumors of the pancreas: correlation of aneuploidy with malignancy and poor prognosis. Cancer. 1996;77:58-62.
148. Vinogradov A, Anatskaya O, Kudryavtsev B. Relationship of hepatocyte ploidy levels with body size and growth rate in mammals. Genome. 2001;44:350-60.
149. Brodsky VY, Delone G. Functional control of hepatocyte proliferation. Comparison with the temporal control of cardiomyocyte proliferation. Biomed Sci. 1990;1:467.
150. Torres S, Díaz BP, Cabrera JJ, Díaz-Chico JC, Díaz-Chico BN, López-Guerra A. Thyroid hormone regulation of rat hepatocyte proliferation and polyploidization. AmJ Physiol Gastrointest Liver Physiol. 1999;276:G155-G63.
151. Klein PA, Xiang J, Kimura AK. Melanoma cells growing in aggregates on a non-adhesive poly (HEMA) substrate exhibit polykaryocytosis but do not develop an increased metastatic capability. Clin Exp Metastasis. 1984;2:287-95.
152. Lu X, Kang Y. Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants. Proceedings of the National Academy of Sciences. 2009;106:9,385.
153. Goldenberg DM, Pavia RA, Tsao MC. In vivo hybridisation of human tumour and normal hamster cells. Nature. 1974;250:649-51.
154. Kerbel RS, Lagarde A, Dennis J, Donaghue T. Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor. Mol Cell Biol. 1983;3:523.
155. Mortensen K, Lichtenberg J, Thomsen P, Larsson LI. Spontaneous fusion between cancer cells and endothelial cells. Cell Mol Life Sci. 2004;61:2,125-31.
156. Jacobsen BM, Harrell JC, Jedlicka P, Borges VF, Varella-Garcia M, Horwitz KB. Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium. Cancer Research. 2006;66:8,274.
157. Smith MA, Bidochka MJ. Bacterial fitness and plasmid loss: the importance of culture conditions and plasmid size. CanJ Microbiol. 1998;44:351-5.
158. Goldenberg DM, Zagzag D, Heselmeyer-Haddad KM, Berroa Garcia LY, Ried T, Loo M, Chang CH, Gold DV. Horizontal transmission and retention of malignancy, as well as functional human genes, after spontaneous fusion of human glioblastoma and hamster host cells in vivo. Int J Cancer. 2012;131:49-58.
159. Aichel O. Ueber Zellverschmelzung mit qualitativ abnormer Chromosomenverteilung als Ursache der Geschwulstbildung, von Prof. Dr. Med. Et phil. Otto Aichel: W. Engelmann; 1911.
160. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1,650.
161. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol. 2009;9:259-70.
162. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16:91-102.
163. Ribatti D, Crivellato E, Roccaro A, Ria R, Vacca A. Mast cell contribution to angiogenesis related to tumour progression. ClinExp Allergy. 2004;34:1,660-4.
164. De Visser KE, Korets LV, Coussens LM. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell. 2005;7:411-23.
165. Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N EnglJ Med. 2004;351:2,159-69.
166. Rizvi AZ, Swain JR, Davies PS, Bailey AS, Decker AD, Willenbring H, Grompe M, Fleming WH, Wong MH. Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. PNAS. 2006;103:6,321-5.
167. Johansson CB, Youssef S, Koleckar K, Holbrook C, Doyonnas R, Corbel SY, Steinman L, Rossi FMV, Blau HM. Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation. Nat Cell Biol. 2008;10:575-83.
168. Nygren JM, Liuba K, Breitbach M, Stott S, Thorén L, Roell W, Geisen C, Sasse P, Kirik D, Björklund A. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol. 2008;10:584-92.
169. Chakraborty A, Lazova R, Davies S, Bäckvall H, Ponten F, Brash D, Pawelek J. Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient. Bone Marrow Transplant. 2004;34:183-6.
170. Andersen TL, Boissy P, Sondergaard T, Kupisiewicz K, Plesner T, Rasmussen T, Haaber J, Kølvraa S, Delaissé J. Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership? J Pathol. 2007;211:10-7.
171. Thiery JP, Acloque H, Huang RYJ, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871-90.
172. Rachkovsky M, Pawelek J. Acquired melanocyte stimulating hormone-inducible chemotaxis following macrophage fusion with Cloudman S91 melanoma cells. Cell Growth & Differentiation: The Molecular Biology Journal of the American Association for Cancer Research. 1999;10:517.
173. Sodi S, Chakraborty A, Platt J, Kolesnikova N, Rosemblat S, Keh-Yen A, Bolognia J, Rachkovsky M, Orlow S, Pawelek J. Melanoma× Macrophage Fusion Hybrids Acquire Increased Melanogenesis and Metastatic Potential: Altered N-Glycosylation as an Underlying Mechanism. Pigment Cell Research. 1998;11:299-309.
174. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4:71-8.
175. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263-6.
176. Bingle L, Brown N, Lewis C. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196(3):254-65.
177. Pollard JW. Macrophages define the invasive microenvironment in breast cancer. J Leukoc Biol. 2008;84:623-30.
178. Chakraborty AK, Kolesnikova N, JdF S, Espreafico EM, Peronni KC, Pawelek J. Expression of c-Met Proto-oncogene in Metastatic Macrophage Melanoma Fusion Hybrids: Implication of Its Possible Role in MSH-Induced Motility. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 2003;14:163-74.
179. Chakraborty AK, Pawelek J, Ikeda Y, Miyoshi E, Kolesnikova N, Funasaka Y, Ichihashi M, Taniguchi N. Fusion hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, β1-6 branching, and metastasis. Cell Growth and Differentiation. 2001;12:623-30.
180. Wright NA. Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer. IntJ Exp Pathol. 2000;81:117-43.
181. Holmgren L, Szeles A, Rajnavölgyi E, Folkman J, Klein G, Ernberg I, Falk KI. Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood. 1999;93:3,956.
182. Bergsmedh A, Szeles A, Henriksson M, Bratt A, Folkman MJ, Spetz AL, Holmgren L. Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proceedings of the National Academy of Sciences. 2001;98:6,407.
183. Al-Nedawi K, Meehan B, Rak J. Messengers and mediators of tumor progression. Cell Cycle. 2009;8:2,014-8.
184. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 2008;10:619-24.
185. Davis DM, Sowinski S. Membrane nanotubes: dynamic long-distance connections between animal cells. Nat Rev Mol Cell Biol. 2008;9:431-6.
186. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Trimmer C, Tsirigos A, Migneco G, Witkiewicz AK, Balliet R. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Cell Cycle. 2010;9:4,297.
187. Wolff JA, Budker V. The mechanism of naked DNA uptake and expression. Adv Genet. 2005;54:1-20.
188. Nagler C, Hardt C, Zänker KS, Dittmar T. Co-cultivation of murine BMDCs with 67NR mouse mammary carcinoma cells give rise to highly drug resistant cells. Cancer Cell Int. 2011;11:21.
189. Kerppola TK. Visualization of molecular interactions by fluorescence complementation. Nat Rev Mol Cell Biol. 2006;7:449-56.
190. Kerppola TK. Bimolecular fluorescence complementation: visualization of molecular interactions in living cells. Methods Cell Biol. 2008;85:431-70.
191. Lin HP, Vincenz C, Eliceiri KW, Kerppola TK, Ogle BM. Bimolecular fluorescence complementation analysis of eukaryotic fusion products. Biol Cell. 2010;102(Pt 9):525.
192. Sprangers A, Freeman B, Kouris N, Ogle B. A Cre-Lox P Recombination Approach for the Detection of Cell Fusion In Vivo. J VisExp: JoVE. 2012;(59):e3581.
193. Kouris NA, Schaefer JA, Hatta M, Kawaoka Y, Kamp TJ, Ogle BM. Directed fusion of mesenchymal stem cells with cardiomyocytes via VSV-G facilitates stem cell programming. Stem Cells Int. 2012;2012:414038.