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Formation of solid tumors by a single multinucleated cancer cell†
Version of Record online: 1 MAR 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 17, pages 4092–4099, 1 September 2011
How to Cite
Weihua, Z., Lin, Q., Ramoth, A. J., Fan, D. and Fidler, I. J. (2011), Formation of solid tumors by a single multinucleated cancer cell. Cancer, 117: 4092–4099. doi: 10.1002/cncr.26021
We thank Rachel Tsan for her excellent technical support; Kenneth Dunner, Jr., for conducting expert transmission electron microscopy; and Arminda Martinez for expert assistance in the preparation of this article.
- Issue online: 19 AUG 2011
- Version of Record online: 1 MAR 2011
- Manuscript Accepted: 26 JAN 2011
- Manuscript Revised: 16 JAN 2011
- Manuscript Received: 20 SEP 2010
- multinucleated cells;
- senescent-like cancer cells;
- cancer-initiating cells
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.
In this study, MNCs were characterized in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at the single-cell level.
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.
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.