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

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.