Zhang Weihua1, Qingtang Lin, Asa J Ramoth, Dominic Fan, Isaiah J Fidler. 1. 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
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. Cancer 2011
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 murinefibrosarcoma 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. Cancer 2011
Authors: G P Dimri; X Lee; G Basile; M Acosta; G Scott; C Roskelley; E E Medrano; M Linskens; I Rubelj; O Pereira-Smith Journal: Proc Natl Acad Sci U S A Date: 1995-09-26 Impact factor: 11.205
Authors: Chenwei Li; David G Heidt; Piero Dalerba; Charles F Burant; Lanjing Zhang; Volkan Adsay; Max Wicha; Michael F Clarke; Diane M Simeone Journal: Cancer Res Date: 2007-02-01 Impact factor: 12.701