Cell-cell fusions and human endogenous retroviruses in cancer

Cell Fusions: Regulation and Control

Volumn , Issue , 2011, Pages 395-426

  Strick, Reiner ^a   Beckmann, Matthias W ^a   Strissel, Pamela L ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Cancer; cell cell fusions; HERV; multinucleated cells; polyploidy; retrovirus; syncytin; virus

Indexed keywords

EID: 84861058287     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-90-481-9772-9_17     Document Type: Chapter

References (239)

1. Ahn K, Kim HS (2009) Structural and quantitative expression analyses of HERV gene family in human tissues. Mol Cells 28:99-103
2. Aichel O (1911) Über Zellverschmelzung mit qualitativ abnormer Chromosomenverteilung als Ursache der Geschwulstbildung. Wilhelm Engelmann, Leipzig
3. Akatsu T, Kameyama K, Kawachi S et al (2006) Gallbladder carcinoma with osteoclast-like giant cells. J Gastroenterol 41:83-87
4. Albores-Saavedra J, Wu J (2006) The many faces and mimics of papillary thyroid carcinoma. Endocr Pathol 17:1-18
5. Al-Hajj M, Clarke MF (2004) Self-renewal and solid tumor stem cells. Oncogene 23:7274-7782
6. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM et al (2003) Fusion of bone marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968-973
7. Alves PM, Lévy N, Stevenson BJ et al (2008) Identification of tumor-Associated antigens by largescale analysis of genes expressed in human colorectal cancer. Cancer Immunol 8:11
8. An DS, Xie YM, Chen IS (2001) Envelope gene of the human endogenous retrovirus HERV-W encodes a functional retrovirus envelope. J Virol 75:3488-3489
9. Andersen TL, Boissy P, Sondergaard TE et al (2007) Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: A new type of cancer-host partnership?. J Pathol 211:10-17
10. Anderson JM (2000) Multinucleated giant cells. Curr Opin Hematol 7:40-47
11. Anderson MJ, Stanbridge EJ (1993) Tumor suppressor genes studied by cell hybridization and chromosome transfer. FASEB J 7:826-833
12. Andersson AC, Svensson AC, Rolny C, Andersson G, Larsson E (1998) Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues. Int J Oncol 12:309-313
13. Antony JM, van Marle G, Opii W et al (2004) Human endogenous retrovirus glycoproteinmediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7:1088-1095
14. Antony JM, Zhu Y, Izad M et al (2007) Comparative expression of human endogenous retrovirus-W genes in multiple sclerosis. AIDS Res Hum Retroviruses 23:1251-1256
15. Armbruester V, Sauter M, Krautkraemer E et al (2002) A novel gene from the human endogenous retrovirus K expressed in transformed cells. Clin Cancer Res 8:1800-1807
16. Athanasou NA, Wells CA, Quinn J et al (1989) The origin and nature of stromal osteoclastlike multinucleated giant cells in breast carcinoma: Implications for tumour osteolysis and macrophage biology. Br J Cancer 59:491-498
17. Atra A, Al-Asiri R, Wali S et al (2007) Hepatocellular carcinoma, syncytial giant cell: A novel variant in children: A case report. Ann Diagn Pathol 11:61-63
18. Avital I, Moreira AL, Klimstra DS et al (2007) Donor-derived human bone marrow cells contribute to solid organ cancers developing after bone marrow transplantation. Stem Cells 25:2903-2909
19. Balada E, Ordi-Ros J, Vilardell-Tarrés M (2009) Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity. Rev Med Virol 19:273-286
20. Bannert N, Kurth R (2004) Retroelements and the human genome: New perspectives on an old relation. Proc Natl Acad Sci USA 101:14572-14579
21. Bar-Shavit Z (2007) The osteoclast: A multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem 102:1130-1139
22. Bieda K, Hoffmann A, Boller K (2001) Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines. J Gen Virol 82:591-596
23. Bjerkvig R, Tysnes BB, Aboody KS et al (2005) Opinion: The origin of the cancer stem cell: Current controversies and new insights. Nat Rev Cancer 5:899-904
24. Bjerregaard B, Holck S, Christensen IJ et al (2006) Syncytin is involved in breast cancerendothelial cell fusions. Cell Mol Life Sci 63:1906-1911
25. Blaak H, vantWout AB, BrouwerM(2000) In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline. Proc Natl Acad Sci USA 97:1269-1274
26. Blaise S, de Parseval N, Bénit L et al (2003) Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 100:13013-13018
27. Blaise S, de Parseval N, Heidmann T (2005) Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes. Retrovirology 2:19
28. Blobel CP,Wolfsberg TG, Turck CWet al (1992) A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 356:248-252
29. Blond JL, Besème F, Duret L et al (1999) Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol 73:1175-1185
30. Boller K, König H, Sauter M et al (1993) Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology 196:349-353
31. Borges M, Bose P, Frank HG et al (2003) A two-colour fluorescence assay for the measurement of syncytial fusion between trophoblast-derived cell lines. Placenta 24:959-964
32. Boros DL (1989) Immunopathology of Schistosoma mansoni infection. Clin Microbiol Rev 2:250-269
33. Boyd AS, Wu H, Shyr Y (2005) Monster cells in malignant melanoma. Am J Dermatopathol 27:208-210
34. Bronson DL, Fraley EE, Fogh J et al (1979) Induction of retrovirus particles in human testicular tumor (Tera-1) cell cultures: An electron microscopic study. J Natl Cancer Inst 63:337-339
35. Budka H (1986) Multinucleated giant cells in brain: A hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 69:253-258
36. BÜscher K, Trefzer U, Hofmann M et al (2005) Expression of human endogenous retrovirus K in melanomas and melanoma cell lines. Cancer Res 65:4172-4180
37. Busund LT, Killie MK, Bartnes K et al (2002) Spontaneously formed tumorigenic hybrids of Meth A sarcoma and macrophages grow faster and are better vascularized than the parental tumor. Int J Cancer 100:407-413
38. Busund LT, Killie MK, Bartnes K et al (2003) Spontaneously formed tumorigenic hybrids of Meth A sarcoma cells and macrophages in vivo. Int J Cancer 106:153-159
39. Camargo FD, FinegoldM, Goodell MA (2004) Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J Clin Invest 113:1266-1270
40. Camargo FD, Green R, Capetanaki Y et al (2003) Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med 9:1520-1527
41. Castedo M, Perfettini JL, Roumier T et al (2004) Cell death by mitotic catastrophe: A molecular definition. Oncogene 23:2825-2837
42. Chakraborty A, Lazova R, Davies S et al (2004) Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient. Bone Marrow Transplant 34:183-186
43. Chakraborty AK, de Freitas Sousa J, Espreafico EM et al (2001) Human monocyte x mouse melanoma fusion hybrids express human gene. Gene 275:103-106
44. Chang C, Chen PT, Chang GD et al (2004) Functional characterization of the placental fusogenic membrane protein syncytin. Biol Reprod 71:1956-1962
45. Chen CP, Chen LF, Yang SR et al (2008) Functional characterization of the human placental fusogenic membrane protein syncytin 2. Biol Reprod 79:815-823
46. Chen EH, Grote E, Mohler W et al (2007) Cell-cell fusion. FEBS Lett 581:2181-2193
47. Cheng JQ, Ruggeri B, Klein WM et al (1996) Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 93:3636-3641
48. Cheynet V, Oriol G, Mallet F (2006) Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein. Retrovirology 3:41
49. Cheynet V, Ruggieri A, Oriol G et al (2005) Synthesis, assembly, and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope. J Virol 79:5585-5593
50. Clement PB, Young RH (2004) Non-endometrioid carcinomas of the uterine corpus: A review of their pathology with emphasis on recent advances and problematic aspects. Adv Anat Pathol 11:117-142
51. Cohen M, Kato N, Larsson E (1988) ERV3 human endogenous provirus mRNAs are expressed in normal and malignant tissues and cells, but not in choriocarcinoma tumor cells. J Cell Biochem 36:121-128
52. Contreras-Galindo R, Kaplan MH, Leissner P et al (2008) Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer. J Virol 82:9329-9336
53. Cowan CA, Atienza J, Melton DA, Eggan K (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369-1373
54. Coyne JD (2007) DCIS and LCIS with multinucleated giant cells-A report of 4 cases. Histopathology 50:669-671
55. Davies PS, Powell AE, Swain JR et al (2009) Inflammation and proliferation act together to mediate intestinal cell fusion. PLoS One 4:e6530
56. De Chiara A, Apice G, Fazioli F et al (1998) Multicentric giant cell tumor with viral-like inclusions associated with Pagets disease of bone: A case treated by steroid therapy. Oncol Rep 5:317-320
57. de Parseval N, Diop G, Blaise S et al (2005) Comprehensive search for intra- And inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: Genes and pseudogenes. BMC Genomics 6:117
58. de Parseval N, Lazar V, Casella JF et al (2003) Survey of human genes of retroviral origin: Identification and transcriptome of the genes with coding capacity for complete envelope proteins. J Virol 77:10414-10422
59. Deckard-Janatpour K, Kragel S, Teplitz RL et al (1998) Tumors of the pancreas with osteoclastlike and pleomorphic giant cells: An immunohistochemical and ploidy study. Arch Pathol Lab Med 122:266-272
60. Depil S, Roche C, Dussart P et al (2002) Expression of a human endogenous retrovirus, HERV-K, in the blood cells of leukemia patients. Leukemia 16:254-259
61. Dewannieux M, Blaise S, Heidmann T (2005) Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. J Virol79:15573-15577
62. Drewlo S, Leyting S, Kokozidou M et al (2006) C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity. Biol Chem 387:1113-1120
63. Drexler HG, Gignac SM, Hoffbrand AV et al (1989) Formation of multinucleated cells in a Hodgkin's-disease-derived cell line. Int J Cancer 43:1083-1090
64. Duelli DM, Hearn S, Myers MP et al (2005) A primate virus generates transformed human cells by fusion. J Cell Biol 171:493-503
65. Duprex WP,McQuaid S, Hangartner L et al (1999) Observation of measles virus cell-To-cell spread in astrocytoma cells by using a green fluorescent protein-expressing recombinant virus. J Virol 73:9568-9575
66. Engel FB, Schebesta M, Keating MT (2006) Anillin localization Defect in cardiomyocyte binucleation. J Mol Cell Cardiol 41:601-612
67. Esnault C, Priet S, Ribet D et al (2008) A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc Natl Acad Sci USA 105:17532-17537
68. Everts V, de Vries TJ, Helfrich MH (2009) Osteoclast heterogeneity: Lessons from osteopetrosis and inflammatory conditions. Biochim Biophys Acta 1792:757-765
69. Factor SM, Biempica L, Ratner I et al (1977) Carcinoma of the breast with multinucleated reactive stromal giant cells. A light and electron microscopic study of two cases. Virchows Arch A Pathol Anat Histol 374:1-12
70. Feng H, Shuda M, Chang Y et al (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096-1100
71. Ferrari G, Cusella-De Angelis G, Coletta M et al (1998) Muscle regeneration by bone marrowderived myogenic progenitors. Science 279:1528-1530
72. Finkeldey W (1931) Über Riesenzellbefunde in Den Gaumenmandeln, zugleich ein Beitrag zur Histopathologie der Mandelveränderungen im Maserninkubationsstadium. Virchows Arch 281:321-329
73. Folpe AL, Mentzel T, Lehr HA et al (2005) Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: A clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 29:1558-1575
74. Frank O, Verbeke C, Schwarz N et al (2008) Variable transcriptional activity of endogenous retroviruses in human breast cancer. J Virol 82:1808-1818
75. Frankel SS, Wenig BM, Burke AP et al (1996) Replication of HIV-1 in Dendritic cell-derived syncytia at the mucosal surface of the adenoid. Science 272:115-117
76. Funakoshi E, Hori T, Haraguchi T et al (2003) Overexpression of the human MNB/DYRK1A gene induces formation of multinucleate cells through overduplication of the centrosome. BMC Cell Biol 4:12
77. Galli R, Binda E, Orfanelli U et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011-7021
78. Ganem NJ, Storchova Z, Pellman D (2007) Tetraploidy, aneuploidy and cancer. Curr Opin Genet Dev 17:157-162
79. Gattegno T, Mittal, A, Valansi, C et al (2007) Genetic control of fusion pore expansion in the epidermis of Caenorhabditis elegans. Mol Biol Cell 18:1153-1166
80. Glotzer M (2001) Animal cell cytokinesis. Annu Rev Cell Dev Biol 17:351-386
81. Goedert JJ, Sauter ME, Jacobson LP et al (1999) High prevalence of antibodies against HERVK10 in patients with testicular cancer but not with AIDS. Cancer Epidemiol Biomarkers Prev 8:293-296
82. Golan M, Hizi A, Resau JH et al (2008) Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker. Neoplasia 10:521-533
83. Goldenberg DM, Pavia RA, Tsao MC (1974) In vivo hybridisation of human tumour and normal hamster cells. Nature 250:649-651
84. Guidotti JE, Brégerie O, Robert A et al (2003) Liver cell polyploidization: A pivotal role for binuclear hepatocytes. J Biol Chem 278:19095-19101
85. Guo GQ, Zheng GC (2004) Hypotheses for the functions of intercellular bridges in male germ cell development and its cellular mechanisms. J Theor Biol 229:139-146
86. Gupta S (2000) Hepatic polyploidy and liver growth control. Semin Cancer Biol 10:161-171
87. Gussoni E, Soneoka Y, Strickland CD et al (1999) Dystrophin expression in the MDX mouse restored by stem cell transplantation. Nature 401:390-394
88. Hahn S, Ugurel S, Hanschmann KM et al (2008) Serological response to human endogenous retrovirus K in melanoma patients correlates with survival probability. AIDS Res Hum Retroviruses 24:717-723
89. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70
90. Hansemann D (1890) Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Arch Pathol Anat etc. Berl (Virchow's Arch) 119:299-326
91. Harris H (1988) The analysis of malignancy by cell fusion: The position in 1988. Cancer Res 48:3302-3306
92. Harris H, Miller OJ, Klein G et al (1969) Suppression of malignancy by cell fusion. Nature 223:363-368
93. Harris H, Watkins JF (1965) Hybrid cells derived from mouse and man: Artificial heterokaryons of mammalian cells from different species. Nature 205:640-646
94. Helm CA, Israelachvili JN,McGuiggan PM (1992) Role of hydrophobic forces in bilayer adhesion and fusion. Biochemistry 31:1794-805
95. Helming L, Gordon S (2007) The molecular basis of macrophage fusion. Immunobiology 212:785-793
96. Herbst H, Sauter M, Mueller-Lantzsch N (1996) Expression of human endogenous retrovirus K elements in germ cell and trophoblastic tumors. Am J Pathol 149: 1727-1735
97. Homma T, Fukushima T, Vaccarella S et al (2006) Correlation among pathology, genotype, and patient outcomes in glioblastoma. J Neuropathol Exp Neurol 65:846-854
98. Horsley V, Pavlath GK (2004) Forming a multinucleated cell: Molecules that regulate myoblast fusion. Cells Tissues Organs 176:67-78
99. Horváth EM, Lacza Z, Csordás A et al (2006) Graft derived cells with double nuclei in the penumbral region of experimental brain trauma. Neurosci Lett 396:182-186
100. Houghton J, Stoicov C, Nomura S et al (2004) Gastric cancer originating from bone marrowderived cells. Science 306:1568-1571
101. Huppertz B. (2009) Review: Biology of the placental syncytiotrophoblast - myths and facts. Placenta. 2009 Dec 29. [Epub ahead of print]
102. Ianus A, Holz GG, Theise ND et al (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111:843-850
103. Ishida T, Obata Y, Ohara N et al (2008) Identification of the HERV-K gag antigen in prostate cancer by SEREX using autologous patient serum and its immunogenicity. Cancer Immun 8:15
104. Jacobsen BM, Harrell JC, Jedlicka P (2006) Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium. Cancer Res 66:8274-8279
105. Jin J, Woodgett JR (2005) Chronic activation of protein kinase Bbeta/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: Events associated with tumorigenesis. Oncogene 24:5459-5470
106. Johansson CB, Youssef S, Koleckar K et al (2008) Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation. Nat Cell Biol 10:575-583
107. Jones MA, Young RH, Scully RE (1991) Endometrial adenocarcinoma with a component of giant cell carcinoma. Int J Gynecol Pathol 10:260-270
108. Jurka J (2000) Repbase update: A database and an electronic journal of repetitive elements. Trends Genet 16:418-20
109. Karlsson H, Bachmann S, Schröder J et al (2001) Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proc Natl Acad Sci USA 98:4634-4639
110. Kerbel RS, Lagarde AE, Dennis JW et al (1983) 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 3:523-538
111. Keydar I, Ohno T, Nayak R et al (1984) Properties of retrovirus-like particles produced by a human breast carcinoma cell line: Immunological relationship with mouse mammary tumor virus proteins. Proc Natl Acad Sci USA 81:4188-4192
112. Kim S, Shilagardi K, Zhang S et al (2007) A critical function for the actin cytoskeleton in targeted exocytosis of prefusion vesicles during myoblast fusion. Dev Cell 12:571-586
113. Kodama S, KÜhtreiber W, Fujimura S et al (2003) Islet regeneration During the reversal of autoimmune diabetes in NOD mice. Science 302:1223-1227
114. Koranda FC (2004) Images in clinical medicine. Use of multinucleated giant cells to diagnose a viral eruption. N Engl J Med 350:e6
115. Krause DS, Theise ND, Collector MI et al (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369-377
116. Krishnan C, Longacre TA (2006) Ductal carcinoma in situ of the breast with osteoclast-like giant cells. Hum Pathol 37:369-372
117. Kudo Y, Boyd CA (2002) Changes in expression and function of syncytin and its receptor, amino acid transport system B(0) (ASCT2), in human placental choriocarcinoma BeWo cells during syncytialization. Placenta 23:536-541
118. Kudryavtsev BN, Kudryavtseva MV, Sakuta GA et al (1993) Human hepatocyte polyploidization kinetics in the course of life cycle. Virchows Arch B Cell Pathol Incl Mol Pathol 64: 387-393
119. KÜppers R (2009) The biology of Hodgkin's lymphoma. Nat Rev Cancer 9:15-27
120. Laforga JB (1999) Giant cell carcinoma of the lung. Report of a case with cytohistologic and clinical correlation. Acta Cytol 43:263-267
121. Lagasse E, Connors H, Al-Dhalimy M et al (2000) Purified hematopoietic stem cells can Differentiate into hepatocytes in vivo. Nat Med 6:1229-1234
122. Langbein M, Strick R, Strissel PL et al (2008) Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev 75:175-183
123. Langhans T (1868) Über Riesenzellen mit wandständigen Kernen in Tuberkeln und die fibröse Form des Tuberkels. Virchows Arch (Pathol Anat) 42:382-404
124. Larizza L, Schirrmacher V (1984) Somatic cell fusion as a source of genetic rearrangement leading to metastatic variants. Cancer Metastasis Rev 3:193-222
125. Larizza L, Schirrmacher V, Pfluger E (1984) Acquisition of high metastatic capacity after in vitro fusion of a nonmetastatic tumor line with a bone marrow-derived macrophage. J Exp Med 160:1579-1584
126. Larsen JM, Christensen IJ, Nielsen HJ et al (2009) Syncytin immunoreactivity in colorectal cancer: Potential prognostic impact. Cancer Lett 280:44-49
127. Larsson LI, Bjerregaard B, Talts JF (2008) Cell fusions in mammals. Histochem Cell Biol 129:551-561
128. Larsson LI, Holck S, Christensen IJ (2007) Prognostic role of syncytin expression in breast cancer. Hum Pathol 38:726-731
129. Lau YS, Danks L, Sun SG et al (2007) RANKL-dependent and RANKL-independent mechanisms of macrophage-osteoclast differentiation in breast cancer. Breast Cancer Res Treat 105:7-16
130. Lau YS, Sabokbar A, Giele H et al (2006) Malignant melanoma and bone resorption. Br J Cancer 94:1496-503
131. Lavillette D, Marin M, Ruggieri A et al (2002) The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol 76:6442-6452
132. Leib-Mösch C, Brack-Werner R, Werner T et al (1990) Endogenous retroviral elements in human DNA. Cancer Res 50:5636S-5642S
133. Lescar J, Roussel A, Wien MW et al (2001) Fusion glycoprotein shell of Semliki Forest virus: An icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105: 137-148
134. Lindeskog M, Blomberg J (1997) Spliced human endogenous retroviral HERV-H env transcripts in T-cell leukaemia cell lines and normal leukocytes: Alternative splicing pattern of HERV-H transcripts. J Gen Virol 78:2575-2585
135. Liu C, Chen Z, Zhang T et al (2006) Multiple tumor types may originate from bone marrow-derived cells. Neoplasia 8:716-724
136. Lordier L, Jalil A, Aurade F et al (2008) Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling. Blood 112:3164-3174
137. Löwer R, Löwer J, Frank H et al (1984) Human teratocarcinomas cultured in vitro produce unique retrovirus-like viruses. J Gen Virol 65:887-898
138. Lu X, Kang Y (2009) Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants. Proc Natl Acad Sci USA 106:9385-9390
139. Maeda K, Mizuno M, Wakabayashi T et al (2003) Morphological assessment of the development of multinucleated giant cells in glioma by using mitosis-specific phosphorylated antibodies. J Neurosurg 98:854-859
140. Malassiné A, Blaise S, Handschuh K et al (2007) Expression of the fusogenic HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted to villous cytotrophoblastic cells. Placenta 28:185-191
141. Mallet F, Bouton O, Prudhomme S et al (2004) The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Proc Natl Acad Sci USA 101:1731-1736
142. Margall-Ducos G, Celton-Morizur S, Couton D et al (2007) Liver tetraploidization is controlled by a new process of incomplete cytokinesis. J Cell Sci 120:3633-3639
143. Margolis RL (2005). Tetraploidy and tumor development. Cancer Cell 8:353-354
144. Matousková M, Blazková J, Pajer P et al (2006) CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. Exp Cell Res 312:1011-1020
145. Matveeva NM, Shilov AG, Kaftanovskaya EM et al (1998) In vitro and in vivo study of pluripotency in intraspecific hybrid cells obtained by fusion of murine embryonic stem cells with splenocytes. Mol Reprod Dev 50:128-138
146. Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J 21:483-492
147. Mi S, Lee X, Li X et al (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403:785-789
148. Miething A (1995) Multinuclearity of germ cells in the senescent human testis originates from a process of cell-cell fusion. J Submicrosc Cytol Pathol 27:105-113
149. Miettinen M, Virtanen I, Talerman A (1985) Intermediate filament proteins in human testis and testicular germ-cell tumors. Am J Pathol 120:402-410
150. Miller FR, McInerney D, Rogers et al (1988) Spontaneous fusion between metastatic mammary tumor subpopulations. J Cell Biochem 36:129-136
151. Miller RA, Ruddle FH (1976) Pluripotent teratocarcinoma-Thymus somatic cell hybrids. Cell 9:45-55
152. Miyoshi Y, Iwao K, Egawa C et al (2001) Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer 92:370-373
153. Mohler WA, Shemer G, del Campo JJ et al (2002) The type I membrane protein EFF-1 is essential for developmental cell fusion. Dev Cell 2:355-362
154. Mortensen K, Lichtenberg J, Thomsen PD et al (2004) Spontaneous fusion between cancer cells and endothelial cells. Cell Mol Life Sci 61:2125-2131
155. Mostofi FK, Sesterhenn IA (1985) Pathology of germ cell tumors of testes. Prog Clin Biol Res 203:1-34
156. Munoz PA, Rao MS, Reddy JK (1980) Osteoclastoma-like giant cell tumor of the liver. Cancer 46:771-779
157. Nakahashi H (1987) Undifferentiated carcinoma of the lung with osteoclast-like giant cells. Jpn J Surg 17:199-203
158. Navarro D, Paz P, Tugizov S et al (1993) Glycoprotein B of human cytomegalovirus promotes virion penetration into cells, transmission of infection from cell to cell, and fusion of infected cells. Virology 197:143-158
159. Nelson PN, Carnegie PR, Martin J et al (2003) Demystified. Human endogenous retroviruses. Mol Pathol 56:11-18
160. Nygren JM, Jovinge S, BreitbachMet al (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10:494-501
161. Nygren JM, Liuba K, Breitbach M et al (2008) Myeloid and lymphoid contribution to nonhaematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol 10:584-592
162. Okamoto H, Mizuno K, Horio T (2003) Monocyte-derived multinucleated giant cells and sarcoidosis. J Dermatol Sci 31:119-128
163. Ono M, Kawakami M, Ushikubo H (1987) Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. J Virol 61:2059-2062
164. Oren-Suissa M, Podbilewicz B (2007) Cell fusion During development. Trends Cell Biol 17:537-546
165. Pathak S, Nemeth MA, Multani AS et al (1997) Can cancer cells transform normal host cells into malignant cells?. Br J Cancer 76:1134-1138
166. Pawelek JM (2005) Tumour-cell fusion as a source of myeloid traits in cancer. Lancet Oncol 6:988-993
167. Pawelek JM, Chakraborty AK (2008) Fusion of tumour cells with bone marrow-derived cells: A unifying explanation for metastasis. Nat Rev Cancer 8:377-386
168. Pesce C, Merino MJ, Chambers JT et al (1991) Endometrial carcinoma with trophoblastic differentiation. An aggressive form of uterine cancer. Cancer 68:1799-1802
169. Piquer-Gil M, García-Verdugo JM, Zipancic I et al (2009) Cell fusion contributes to pericyte formation after stroke. J Cereb Blood Flow Metab 29:480-485
170. Prudhomme S, Oriol G, Mallet F (2004) A retroviral promoter and a cellular enhancer define a bipartite element which controls Env ERVWE1 placental expression. J Virol 78:12157-12168
171. Prusty BK, zur Hausen H, Schmidt R et al (2008) Transcription of HERV-E and HERV-Erelated sequences in malignant and non-malignant human haematopoietic cells. Virology 382: 37-45
172. Rakowicz-Szulczynska EM, McIntosh DG, Smith ML (1999) Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid. Clin Diagn Lab Immunol 6:115-126
173. Ravid K, Lu J, Zimmet JM, Jones MR (2002) Roads to polyploidy: The megakaryocyte example. J Cell Physiol 190:7-20
174. Razzuk MA, Urschel HC Jr, Albers JE et al (1976) Pulmonary giant cell carcinoma. Ann Thorac Surg 21:540-545
175. Reinecke H, Minami E, Poppa V et al (2004) Evidence for fusion between cardiac and skeletal muscle cells. Circ Res 94:e56-e60
176. Rizvi AZ, Swain JR, Davies PS et al (2006) Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. Proc Natl Acad Sci USA 103:6321-6325
177. Robinson LR, Damjenov I, Brezina P (1977) Multinucleated giant cell neoplasm of pancreas. Arch Pathol Lab Med 101:590-593
178. Rodi'c N, Rutenberg MS, Terada N (2004) Cell fusion and reprogramming: Resolving our transdifferences. Trends Mol Med 10:93-96
179. Roger V, Nasiell M, Nasiell K et al (1972) Cytologic findings indicating pulmonary tuberculosis. II. The occurrence in sputum of epithelioid cells and multinucleated giant cells in pulmonary tuberculosis, chronic non-Tuberculous inflammatory lung disease and bronchogenic carcinoma. Acta Cytol 16:538-542
180. Roodman GD, Windle JJ (2005) Paget disease of bone. J Clin Invest 115:200-208
181. Saltel F, Chabadel A, Zhao Y et al (2006) Transmigration: A new property of mature multinucleated osteoclasts. J Bone Miner Res 21:1913-1923
182. Schleiden MJ (1838) Beiträge zur Phytogenesis. Archiv fÜr Anatomie, Physiologie und wissenschaftliche Medicin 13:137-176
183. Schmitz-Winnenthal FH, Galindo-Escobedo LV, Rimoldi D et al (2007) Potential target antigens for immunotherapy in human pancreatic cancer. Cancer Lett 252:290-298
184. Schwann T (1839) Mikroskopische Untersuchungen Über die Übereinstimmung in Der Struktur und dem Wachstum der Thiere und Pflanzen. Sander (Reimer), Berlin
185. Serafino A, Balestrieri E, Pierimarchi P et al (2009) The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation. Exp Cell Res 315:849-862
186. Shabo I, Olsson H, Sun XF et al (2009) Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer 125:1826-1831
187. Shemer G, Podbilewicz B (2003) The story of cell fusion: Big lessons from little worms. Bioessays 25:672-682
188. Shestopalov VI, Bassnett S (2000) Expression of autofluorescent proteins reveals a novel protein permeable pathway between cells in the lens core. J Cell Sci 113:1913-1921
189. Shi Y, Barton K, De Maria A et al (2009) The stratified syncytium of the vertebrate lens. J Cell Sci 122:1607-1615
190. Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396-401
191. Skehel JJ, Wiley DC (1998) Coiled coils in both intracellular vesicle and viral membrane fusion. Cell 95:871-874
192. Stanbridge EJ (1976) Suppression of malignancy in human cells. Nature 260:17-20
193. Stanbridge EJ, Der CJ, Doersen CJ et al (1982) Human cell hybrids: Analysis of transformation and tumorigenicity. Science 215:252-259
194. Stauffer Y, Theiler G, Sperisen P et al (2004) Digital expression profiles of human endogenous retroviral families in normal and cancerous tissues. Cancer Immunol 4:2
195. Strick R, Ackermann S, Langbein M et al (2007) Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral Syncytin-1 and regulated by TGFbeta. J Mol Med 85:23-38
196. Tada M, Takahama Y, Abe K et al (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11:1553-1558
197. Takeuchi H, Kubota T, Kitai R et al (2008) CD98 immunoreactivity in multinucleated giant cells of glioblastomas: An immunohistochemical double labeling study. Neuropathology 28:127-131
198. Takeuchi H, Sato K, Ido K et al (2006) Mitotic activity of multinucleated giant cells with glial fibrillary acidic protein immunoreactivity in-18 glioblastomas: An immunohistochemical double labeling study. J Neurooncol 78:15
199. Terada N, Hamazaki T, Oka M et al (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416:542-545
200. Therman E, Sarto GE, Buchler DA (1983) The structure and origin of giant nuclei in human cancer cells. Cancer Genet Cytogenet 9:9-18
201. Tran SD, Pillemer SR, Dutra A et al (2003) Differentiation of human bone
202. Tristem M (2000) Identification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the human genome mapping project database. J Virol 74:3715-3730
203. Turbeville MA, Rhodes JC, Hyams DM et al (1997) Characterization of a putative retroviral envrelated human protein. Pathobiology 65:123-128
204. Turner G, Barbulescu M, Su M et al (2001) Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr Biol 11:1531-1535
205. Ulbright TM (2005) Germ cell tumors of the gonads: A selective review emphasizing problems in Differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 18: S61-S79
206. Ullah Z, Kohn MJ, Yagi R et al (2008) Differentiation of trophoblast stem cells into giant cells is triggered by p57/Kip2 inhibition of CDK1 activity. Genes Dev 22:3024-3036
207. Vassilopoulos G, Wang PR, Russell DW (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901-904
208. Veliath AJ, Sandaran V, Aurora AM (1975) Ovarian giant cell tumor with cystadenocarcinoma. Arch Pathol 99:488-491
209. Vignery A (2005) Macrophage fusion: Are somatic and cancer cells possible partners?. Trends Cell Biol 15:188-193
210. Villesen P, Aagaard L, Wiuf C et al (2004) Identification of endogenous retroviral reading frames in the human genome. Retrovirology 1:32
211. von Hochstetter AR, Sigg C, Saremaslani P et al (1985) The significance of giant cells in human testicular seminomas. A clinico-pathological study. Virchows Arch A Pathol Anat Histopathol 407:309-322
212. Wang X,Willenbring H, Akkari Y et al (2003) Cell fusion is the principal source of bone-marrowderived hepatocytes. Nature 422:897-901
213. Wang-Johanning F, Frost AR, Jian B et al (2003) Detecting the expression of human endogenous retrovirus E envelope transcripts in human prostate adenocarcinoma. Cancer 98:187-197
214. Wang-Johanning F, Frost AR, Jian B et al (2003) Quantitation of HERV-K env gene expression and splicing in human breast cancer. Oncogene 22:1528-1535
215. Wang-Johanning F, Frost AR, Johanning GL et al (2001) Expression of human endogenous retrovirus k envelope transcripts in human breast cancer. Clin Cancer Res 7:1553-1560
216. Wang-Johanning F, Liu J, Rycaj K et al (2007) Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. Int J Cancer 120:81-90
217. Wang-Johanning F, Radvanyi L, Rycaj K et al (2008) Human endogenous retrovirus K triggers an antigen-specific immune response in breast cancer patients. Cancer Res 68:5869-5877
218. Watanabe K, Hiraki H, Ohishi M et al (1996) Uterine leiomyosarcoma with osteoclast-like giant cells: Histopathological and cytological observations. Pathol Int 46:656-660
219. Weimann JM, Johansson CB, Trejo A et al (2003) Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nat Cell Biol 5:959-966
220. Werner M (2006) Giant cell tumour of bone: Morphological, biological and histogenetical aspects. Int Orthop 30:484-489
221. Wiener F, Klein G, Harris H (1974a) The analysis of malignancy by cell fusion. V. Further evidence of the ability of normal diploid cells to suppress malignancy. J Cell Sci 15:177-183
222. Wiener F, Klein G, Harris H (1974b) The analysis of malignancy by cell fusion. VI. Hybrids between Different tumour cells. J Cell Sci 16:189-198
223. Williams WJ, Williams D (1967) 'Residual bodies' in sarcoid and sarcoid-like granulomas. J Clin Pathol 20:574-577
224. Winge O (1927) Cytologische Untersuchungen Über die Natur maligner Tumoren I. Z. Zellforschg 6
225. Wöckel L, Ketelsen UP, Stötter M et al (1998) Abundant minute myotubes in a patient who later developed centronuclear myopathy. Acta Neuropathol 95:547-551
226. Yasunaga M, Ohishi Y, Nishimura I et al (2008) Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung. Pathol Int 58:244-248
227. Yesner R (1985) Large cell carcinoma of the lung. Semin Diagn Pathol 2:255-269
228. Yi JM, Kim HM, Kim HS (2004) Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells. J Gen Virol 85:1203-1210
229. Yi JM, Kim HM, Kim HS (2006) Human endogenous retrovirus HERV-H family in human tissues and cancer cells: Expression, identification, and phylogeny. Cancer Lett 231:228-239
230. Yi JM, Kim HS (2004) Expression analysis of endogenous retroviral elements belonging to the HERV-F family from human tissues and cancer cells. Cancer Lett 211:89-96
231. Yi JM, Kim HS (2007) Expression and phylogenetic analyses of human endogenous retrovirus HC2 belonging to the HERV-T family in human tissues and cancer cells. J Hum Genet 52: 285-296
232. Yi JM, Kim HS (2007) Molecular phylogenetic analysis of the human endogenous retrovirus E (HERV-E) family in human tissues and human cancers. Genes Genet Syst 82:89-98
233. Yi JM, Kim TH, Huh JW et al (2004) Human endogenous retroviral elements belonging to the HERV-S family from human tissues, cancer cells, and primates: Expression, structure, phylogeny and evolution. Gene 342:283-292
234. Yi JM, Lee WH, Kim HM et al (2001) Identification of new endogenous retroviral sequences belonging to the HERV-W family in human cancer cells. Intervirology 44:333-338
235. Yi JM, Schuebel K, Kim HS (2007) Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P family in primates, human tissues, and cancer cells. Genomics 89:1-9
236. Yilmaz Y, Lazova R, Qumsiyeh M et al (2005) Donor Y chromosome in renal carcinoma cells of a female BMT recipient: Visualization of putative BMT-Tumor hybrids by FISH. Bone Marrow Transplant 35:1021-1024
237. Ying QL, Nichols J, Evans EP et al (2002) Changing potency by spontaneous fusion. Nature 416:545-548
238. Zhivotovsky B, Kroemer G (2004) Apoptosis and genomic instability. Nat Rev Mol Cell Biol 5:752-762
239. Zhou H, Kuang J, Zhong L et al (1998) Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 20:189-193