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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, CY
Published in: Journal of Investigative Dermatology
January 1, 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 E 2 (PGE 2). Our study therefore suggests a counterintuitive strategy to inhibit caspase 3 for therapeutic gain in melanoma treatment.

Duke Scholars

Published In

Journal of Investigative Dermatology

DOI

EISSN

1523-1747

ISSN

0022-202X

Publication Date

January 1, 2014

Volume

134

Issue

6

Start / End Page

1686 / 1692

Related Subject Headings

  • Dermatology & Venereal Diseases
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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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. Journal of Investigative Dermatology, 134(6), 1686–1692. https://doi.org/10.1038/jid.2014.18
Donato, A. L., Q. Huang, X. Liu, F. Li, M. A. Zimmerman, and C. Y. Li. “Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.” Journal of Investigative Dermatology 134, no. 6 (January 1, 2014): 1686–92. https://doi.org/10.1038/jid.2014.18.
Donato AL, Huang Q, Liu X, Li F, Zimmerman MA, Li CY. Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. Journal of Investigative Dermatology. 2014 Jan 1;134(6):1686–92.
Donato, A. L., et al. “Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.” Journal of Investigative Dermatology, vol. 134, no. 6, Jan. 2014, pp. 1686–92. Scopus, doi:10.1038/jid.2014.18.
Donato AL, Huang Q, Liu X, Li F, Zimmerman MA, Li CY. Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. Journal of Investigative Dermatology. 2014 Jan 1;134(6):1686–1692.
Journal cover image

Published In

Journal of Investigative Dermatology

DOI

EISSN

1523-1747

ISSN

0022-202X

Publication Date

January 1, 2014

Volume

134

Issue

6

Start / End Page

1686 / 1692

Related Subject Headings

  • Dermatology & Venereal Diseases
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences