Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.

Published

Journal Article

Metastatic melanoma often relapses despite cytotoxic treatment, and hence the understanding of melanoma tumor repopulation is crucial for improving our current therapies. In this study, we aim to define the role of caspase 3 in melanoma tumor growth after cytotoxic therapy. We examined a paradigm-changing hypothesis that dying melanoma cells undergoing apoptosis during cytotoxic treatment activate paracrine signaling events that promote the growth of surviving tumor cells. We propose that caspase 3 has a key role in the initiation of the release of signals from dying cells to stimulate melanoma tumor growth. We created a model for tumor cell repopulation in which a small number of luciferase-labeled, untreated melanoma cells are seeded onto a layer of a larger number of unlabeled, lethally treated melanoma cells. We found that dying melanoma cells significantly stimulate the growth of living melanoma cells in vitro and in vivo. Furthermore, we observed that caspase 3 gene knockdown attenuated the growth-stimulating effect of irradiated, dying cells on living melanoma cell growth. Finally, we showed that caspase 3-mediated dying melanoma cell stimulation of living cell growth involves secreted prostaglandin E2 (PGE2). Our study therefore suggests a counterintuitive strategy to inhibit caspase 3 for therapeutic gain in melanoma treatment.

Full Text

Duke Authors

Cited Authors

  • Donato, AL; Huang, Q; Liu, X; Li, F; Zimmerman, MA; Li, C-Y

Published Date

  • June 2014

Published In

Volume / Issue

  • 134 / 6

Start / End Page

  • 1686 - 1692

PubMed ID

  • 24434746

Pubmed Central ID

  • 24434746

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

Digital Object Identifier (DOI)

  • 10.1038/jid.2014.18

Language

  • eng

Conference Location

  • United States