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Nat Med. 2011 Jul 3;17(7):860-6. doi: 10.1038/nm.2385.

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.

Author information

1
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.

PMID:
21725296
PMCID:
PMC3132290
DOI:
10.1038/nm.2385
[Indexed for MEDLINE]
Free PMC Article

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