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Formation of solid tumors by a single multinucleated cancer cell
Author(s) -
Weihua Zhang,
Lin Qingtang,
Ramoth Asa J.,
Fan Dominic,
Fidler Isaiah J.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26021
Subject(s) - peripheral blood mononuclear cell , cancer research , in vivo , clonogenic assay , fibrosarcoma , multinucleate , cell culture , medicine , ht1080 , carcinogenesis , in vitro , cell , cancer , pathology , biology , biochemistry , genetics , microbiology and biotechnology
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. © 2011 American Cancer Society.