Radiation response and cellular re-population kinetics of thymocytes in neonatal B6C3F1 mice.

Murine thymic lymphoma (TL) is a suitable model for studying the causative genes of human T-cell acute lymphoblastic leukemia (T-ALL) and radiation-lymphomagenesis. Risk of radiation-induced thymic lymphoma is dependent on the age at exposure. Incidence of thymic lymphoma after whole-body irradiation of neonate (one week-old) B6C3F1 mice is higher than that for adults (seven weeks of age). However, the mechanism(s) of susceptibility for neonates is unknown. In this study, we aimed to clarify age-dependent changes in thymocyte re-population kinetics and cellular responses to radiation, to shed light on the age effect for radiation carcinogenesis. After 4 Gy whole-body gamma-irradiation, the total number of thymocytes dramatically decreased and then increased in two waves. Cellular re-population especially CD4-CD8- cells was more immediate after neonate irradiation (day 4-10, day 14-25) than after adult irradiation (day 5-10, day 23-35). Apoptosis was delayed in neonates (6 h after irradiation) compared to adults (3 h), but cell proliferation persisted longer in neonates (6 h) than in adults (3 h). These differences in radiation response and recovery of thymocytes after irradiation may account for in part the higher susceptibility of the neonatal thymus to radiation carcinogenesis.6th International Workshop of Kyoto T Cell Conferenc

Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage

Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage