Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy |
| |
Authors: | Huang Qian Li Fang Liu Xinjian Li Wenrong Shi Wei Liu Fei-Fei O'Sullivan Brian He Zhimin Peng Yuanlin Tan Aik-Choon Zhou Ling Shen Jingping Han Gangwen Wang Xiao-Jing Thorburn Jackie Thorburn Andrew Jimeno Antonio Raben David Bedford Joel S Li Chuan-Yuan |
| |
Institution: | Experimental Research Center, First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. |
| |
Abstract: | In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopulation of tumors undergoing radiotherapy. Furthermore, activated caspase 3, a key executioner in apoptosis, is involved in the growth stimulation. One downstream effector that caspase 3 regulates is prostaglandin E(2) (PGE(2)), which can potently stimulate growth of surviving tumor cells. Deficiency of caspase 3 either in tumor cells or in tumor stroma caused substantial tumor sensitivity to radiotherapy in xenograft or mouse tumors. In human subjects with cancer, higher amounts of activated caspase 3 in tumor tissues are correlated with markedly increased rate of recurrence and death. We propose the existence of a cell death-induced tumor repopulation pathway in which caspase 3 has a major role. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|