State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, People's Republic of China.
Br J Cancer. 2012 Apr 24;106(9):1512-9. doi: 10.1038/bjc.2012.126.
Cancer stem cells (CSCs) paradigm suggests that CSCs might have important clinical implications in cancer therapy. Previously, we reported that accumulation efficiency of CSCs is different post low- and high-LET irradiation in 48 h.
Cancer stem cells and non-stem cancer cells (NSCCs) were sorted and functionally identified through a variety of assays such as antigen profiles and sphere formation. Inter-conversion between CSCs and NSCCs were in situ visualised. Cancer stem cells proportions were assayed over multiple generations under normal and irradiation surroundings. Supplement and inhibition of TGF-β1, as well as immunofluorescence assay of E-cadherin and Vimentin, were performed.
Surface antigen markers of CSCs and NSCCs exist in an intrinsic homoeostasis state with spontaneous and in situ visualisable inter-conversions, irrespective of prior radiations. Supplement with TGF-β1 accelerates the equilibrium, whereas inhibition of TGF-β signalling disturbs the equilibrium and significantly decreases CSC proportion. Epithelial mesenchymal transition (EMT) might be activated during the process.
Our results indicate that the intrinsic inter-conversion and dynamic equilibrium between CSCs and NSCCs exist under normal and irradiation surroundings, and TGF-β might have important roles in the equilibrium through activating EMT.
癌症干细胞（CSC）理论表明，CSC 可能对癌症治疗具有重要的临床意义。此前，我们报道过在低 LET 和高 LET 照射后 48 小时，CSC 的积累效率不同。
通过各种检测，如抗原谱和球体形成，对 CSC 和非干细胞癌细胞（NSCC）进行分选和功能鉴定。CSC 和 NSCC 之间的相互转化可以在原位可视化。在正常和照射环境下，对多个代次的 CSC 比例进行检测。进行 TGF-β1 的补充和抑制，以及 E-钙黏蛋白和波形蛋白的免疫荧光检测。
CSC 和 NSCC 的表面抗原标志物处于内在的同源平衡状态，具有自发的和原位可视化的相互转化，而与先前的辐射无关。TGF-β1 的补充加速了这种平衡，而 TGF-β 信号通路的抑制则破坏了平衡，并显著降低了 CSC 的比例。在此过程中可能激活上皮间质转化（EMT）。
我们的结果表明，CSC 和 NSCC 之间存在内在的相互转化和动态平衡，TGF-β 通过激活 EMT 在平衡中可能具有重要作用。
