Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, College of Natural Science and Mathematics, University of Houston, Houston, Texas, USA.
Cancer. 2011 Sep 1;117(17):4092-9. doi: 10.1002/cncr.26021. Epub 2011 Mar 1.
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.
在广泛用于研究的致瘤性癌细胞系中，通常存在多核巨细胞（MNC）。然而，MNC 对肿瘤发生的贡献尚不清楚。
本研究在体外和体内单细胞水平上对鼠纤维肉瘤细胞系 UV-2237 中的 MNC 进行了表征。
作者观察到 MNC 起源于单核细胞的罕见亚群，并且对衰老标志物β-半乳糖苷酶呈阳性。此外，当在硬琼脂中培养时，MNC 负责大多数集落形成活性；它们比单核细胞对化疗药物更具抵抗力；它们可以在体外和体内进行不对称分裂（产生单核细胞）和自我更新；最重要的是，单个 MNC 产生了原位、皮下肿瘤（主要由单核细胞组成），这些肿瘤在裸鼠中自发产生肺转移。
目前的结果表明，MNC 的生长可能在应激下被阻断，并且 MNC 对化疗具有高度抗性，可以产生克隆、原位、转移性肿瘤。
