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

Publication ,  Journal Article
Donato, AL; Huang, Q; Liu, X; Li, F; Zimmerman, MA; Li, C-Y
Published in: J Invest Dermatol
June 2014

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.

Duke Scholars

Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

June 2014

Volume

134

Issue

6

Start / End Page

1686 / 1692

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Recurrence
  • Neoplasm Transplantation
  • Microscopy, Fluorescence
  • Mice, Nude
  • Mice
  • Melanoma
  • Male
  • Luciferases
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Donato, A. L., Huang, Q., Liu, X., Li, F., Zimmerman, M. A., & Li, C.-Y. (2014). Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. J Invest Dermatol, 134(6), 1686–1692. https://doi.org/10.1038/jid.2014.18
Donato, Anne L., Qian Huang, Xinjian Liu, Fang Li, Mary A. Zimmerman, and Chuan-Yuan Li. “Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.J Invest Dermatol 134, no. 6 (June 2014): 1686–92. https://doi.org/10.1038/jid.2014.18.
Donato AL, Huang Q, Liu X, Li F, Zimmerman MA, Li C-Y. Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. J Invest Dermatol. 2014 Jun;134(6):1686–92.
Donato, Anne L., et al. “Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.J Invest Dermatol, vol. 134, no. 6, June 2014, pp. 1686–92. Pubmed, doi:10.1038/jid.2014.18.
Donato AL, Huang Q, Liu X, Li F, Zimmerman MA, Li C-Y. Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. J Invest Dermatol. 2014 Jun;134(6):1686–1692.
Journal cover image

Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

June 2014

Volume

134

Issue

6

Start / End Page

1686 / 1692

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Recurrence
  • Neoplasm Transplantation
  • Microscopy, Fluorescence
  • Mice, Nude
  • Mice
  • Melanoma
  • Male
  • Luciferases
  • Humans