ホジキンリンパ腫における小型腫瘍細胞と造腫瘍能

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  • Role of small-sized tumor cells in Hodgkin lymphoma tumorigenicity

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<p>Tumors consist of heterogeneous cell populations derived from a single clone. Recently, it has been demonstrated that tumor cells with tumorigenic potential are limited to a small population, called cancer-initiating cells (CICs), in several tumors, such as leukemia, breast, brain, and colon cancers. CICs efficiently efflux anti-tumor chemicals, degradate reactive oxygen species (ROS) and have high aldehyde dehydrogenase (ALDH) activity. To date, such kind of population has not been identified in malignant lymphomas. Here, we examined the presence of such population in Hodgkin lymphoma cell lines from viewpoint of ROS level. Hodgkin lymphoma cell lines L1236 and L428 consist of heterogeneous sized cells; single-nucleated small-sized cells (S cells) and multinucleated large-sized cells (M cells) like Reed-Sternberg cells. In semi-solid cultures and NOD/SCID mice injection, S cells formed colonies and tumors more efficiently than M cells. A part of S cells contained lower levels of ROS than M cells. ROS-low cells also formed colonies and tumors more efficiently than ROS-high cells. The expression of FoxO3a, a transcription factor regulating ROSdegrading enzymes, was higher in ROS-low populations than in ROS-high. These findings suggest that ROS-low S cells might play an important role in tumorigenesis of Hodgkin lymphoma.</p>

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