title: Formation of solid tumors by a single multinucleated cancer cell.
abstract: BACKGROUND
  Large multinucleated cells (MNCs) commonly exist in tumorigenic cancer cell lines that are used widely in research. However, the contributions of MNCs to tumorigenesis are unknown.
  
  
  METHODS
  In this study, MNCs were characterized in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at the single-cell level.
  
  
  RESULTS
  The authors observed that MNCs originated from a rare subpopulation of mononuclear cells and were positive for a senescent marker, β-galactosidase. In addition, MNCs were responsible for the majority of clonogenic activity when cultured in hard agar; they were more resistant to chemotherapeutic agents than mononuclear cells; they could undergo asymmetric division (producing mononuclear cells) and self-renewal in vitro and in vivo; and, most important; a single MNC produced orthotopic, subcutaneous tumors (composed mainly of mononuclear cells) that gave rise to spontaneous lung metastases in nude mice.
  
  
  CONCLUSIONS
  The current results indicated that the growth of MNCs may be arrested under stress and that MNCs are highly resistant to chemotherapy and can generate clonal, orthotopic, metastatic tumors.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, College of Natural Science and Mathematics, University of Houston, Houston, Texas, USA. wzhang13@uh.edu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Weihua
authors.forename: Qingtang
authors.initials: Q
authors.lastname: Lin
authors.forename: Asa J
authors.initials: AJ
authors.lastname: Ramoth
authors.forename: Dominic
authors.initials: D
authors.lastname: Fan
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D002999:Clone Cells; D005354:Fibrosarcoma / Q000473:pathology*; D015726:Giant Cells / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012878:Skin Neoplasms / Q000209:etiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase