Genotoxic stress induces Sca-1-expressing metastatic mammary cancer cells

Jianlin Gong, Benjamin J. Lang, Desheng Weng, Takanori Eguchi, Ayesha Murshid, Thiago J. Borges, Sachin Doshi, Baizheng Song, Mary A. Stevenson, Stuart K. Calderwood

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Abstract

We describe a cell damage-induced phenotype in mammary carcinoma cells involving acquisition of enhanced migratory and metastatic properties. Induction of this state by radiation required increased activity of the Ptgs2 gene product cyclooxygenase 2 (Cox2), secretion of its bioactive lipid product prostaglandin E2 (PGE2), and the activity of the PGE2 receptor EP4. Although largely transient, decaying to low levels in a few days to a week, this phenotype was cumulative with damage and levels of cell markers Sca-1 and ALDH1 increased with treatment dose. The Sca-1+, metastatic phenotype was inhibited by both Cox2 inhibitors and PGE2 receptor antagonists, suggesting novel approaches to radiosensitization.

Original languageEnglish
Pages (from-to)1249-1263
Number of pages15
JournalMolecular Oncology
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 1 2018
Externally publishedYes

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Keywords

  • genotoxic stress
  • radiation bystander effect
  • radiation therapy
  • responses to cancer therapy
  • Sca-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cancer Research

Cite this

Gong, J., Lang, B. J., Weng, D., Eguchi, T., Murshid, A., Borges, T. J., Doshi, S., Song, B., Stevenson, M. A., & Calderwood, S. K. (2018). Genotoxic stress induces Sca-1-expressing metastatic mammary cancer cells. Molecular Oncology, 12(8), 1249-1263. https://doi.org/10.1002/1878-0261.12321