Genotoxic stress induces Sca‐1‐expressing metastatic mammary cancer cells. Issue 8 (13th June 2018)

• Record Type: Journal Article
• Authors: Gong, Jianlin; Lang, Benjamin J.; Weng, Desheng; Eguchi, Takanori; Murshid, Ayesha; Borges, Thiago J.; Doshi, Sachin; Song, Baizheng; Stevenson, Mary A.; Calderwood, Stuart K.
• Is Part Of: Molecular oncology. Volume 12:Issue 8(2018)
• Page Start: 1249
• Page End: 1263
• Publication Date: 2018-06-13
• Subjects: genotoxic stress -- radiation bystander effect -- radiation therapy -- responses to cancer therapy -- Sca‐1; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12321
• Languages: English
• ISSNs: 1574-7891

Abstract

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. Abstract : The study demonstrates the enrichment of a Sca1+ALDH+ migratory phenotype in irradiated mammary carcinoma cells and in nontreated cells exposed to factors released from irradiated 4T1 cells. This molecular presentation is shown to closely associate with enhanced metastasis to draining lymph nodes in vivo and to be dependent upon Cox2‐prostaglandin E2 signaling, underscoring a potential adjuvant target for radiation therapy.