Formation of solid tumors by a single multinucleated cancer cell.

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.