Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy
- PMID: 21725296
- PMCID: PMC3132290
- DOI: 10.1038/nm.2385
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.
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Comment in
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A downside to apoptosis in cancer therapy?Nat Med. 2011 Jul 7;17(7):780-2. doi: 10.1038/nm0711-780. Nat Med. 2011. PMID: 21738153 No abstract available.
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Radiotherapy: Repopulating tumor cells--dying for caspase 3.Nat Rev Clin Oncol. 2011 Jul 26;8(9):508. doi: 10.1038/nrclinonc.2011.112. Nat Rev Clin Oncol. 2011. PMID: 21788972 No abstract available.
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