Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.
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.
Huang, Q; Li, F; Liu, X; Li, W; Shi, W; Liu, F-F; O'Sullivan, B; He, Z; Peng, Y; Tan, A-C; Zhou, L; Shen, J; Han, G; Wang, X-J; Thorburn, J; Thorburn, A; Jimeno, A; Raben, D; Bedford, JS; Li, C-Y
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