title: Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.
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.
authors: Experimental Research Center, First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Qian
authors: Q
authors: Huang
authors: Fang
authors: F
authors: Li
authors: Xinjian
authors: X
authors: Liu
authors: Wenrong
authors: W
authors: Li
authors: Wei
authors: W
authors: Shi
authors: Fei-Fei
authors: FF
authors: Liu
authors: Brian
authors: B
authors: O'Sullivan
authors: Zhimin
authors: Z
authors: He
authors: Yuanlin
authors: Y
authors: Peng
authors: Aik-Choon
authors: AC
authors: Tan
authors: Ling
authors: L
authors: Zhou
authors: Jingping
authors: J
authors: Shen
authors: Gangwen
authors: G
authors: Han
authors: Xiao-Jing
authors: XJ
authors: Wang
authors: Jackie
authors: J
authors: Thorburn
authors: Andrew
authors: A
authors: Thorburn
authors: Antonio
authors: A
authors: Jimeno
authors: David
authors: D
authors: Raben
authors: Joel S
authors: JS
authors: Bedford
authors: Chuan-Yuan
authors: CY
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D054522:Group VI Phospholipases A2 / Q000378:metabolism; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000532:radiotherapy*
chemical_list: D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse; D053148:Caspase 3; D015232:Dinoprostone