Figure 5. Tumorigenic potential of dedifferentiated tumor cells in vivo.
(A) In vivo tumorigenic analysis strategies. The 14 d hypoxia (1%) or normoxia (21%) exposed CD133−CD15−NESTIN− Gl261-luc cells (104) were injected into the brains of female C57 mice. These mice were raised under normoxia (21% O2). Alternatively, the mice were intracerebrally injected with normoxia-treated CD133−CD15−NESTIN− Gl261-luc cells (3 × 104) and subsequently raised under hypoxia (10% O2) or normoxia (21% O2). (B) GL261 cells following 14 d of in vitro hypoxia (1% O2) had a stronger tumorigenic ability compared with the normoxia cells. The mice with in vivo injections of differentiated CD133−CD15−NESTIN− cells that were raised under hypoxia (10% O2) exhibited a stronger tumorigenic ability compared with the mice raised under normoxia. (C) The quantitative value of bioluminescence was significantly increased in hypoxia compared with normoxia (*P < 0.001, Paired-samples T Test). (D) Lethality analysis indicated there were significant higher death rates in hypoxia-exposed cell injection than normoxia-exposed cell injection, the same trend was found between the mice with normoxia-exposed cells raised under normoxia or hypoxia (Log-rank Test).