Open AccessGenotoxic stress induces Sca‐1‐expressing metastatic mammary cancer cells
Author(s) -
Gong Jianlin,
Lang Benjamin J.,
Weng Desheng,
Eguchi Takanori,
Murshid Ayesha,
Borges Thiago J.,
Doshi Sachin,
Song Baizheng,
Stevenson Mary A.,
Calderwood Stuart K.
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12321
Subject(s) - phenotype , cancer research , prostaglandin e2 , biology , prostaglandin , receptor , cancer cell , cell , medicine , endocrinology , cancer , gene , biochemistry
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 ( PGE 2), and the activity of the PGE 2 receptor EP 4. 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 ALDH 1 increased with treatment dose. The Sca‐1 + , metastatic phenotype was inhibited by both Cox2 inhibitors and PGE 2 receptor antagonists, suggesting novel approaches to radiosensitization.