Identification of novel therapeutic targets in the secretome of ionizing radiation  -induced senescent XXXX cells.

@entity1 @entity34830 @entity986 @entity5 @entity2204 @entity4222 @entity3207 @entity2159
UNASSIGNED: Cellular senescence is a state of irreversible growth arrest that can be triggered by multiple mechanisms, including telomere @entity3207 , the epigenetic derepression of the @entity986 locus and DNA damage. Senescence has been considered a @entity5  -suppressing mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells have deleterious effects on the tissue microenvironment. Some of these effects could be attributed to the senescence  -associated secretory phenotype that has the ability to promote @entity5 progression. However, secreted proteins from senescent @entity5 cells and their effects on the @entity5 microenvironment due to ionizing radiation (IR) exposure have not yet been fully elucidated. In the present study, we analyzed cytokines secreted from IR  -induced senescent MCF7 cells by using cytokine microarrays and confirmed by western blot analysis that increased secretion of @entity2159 ( @entity2159 ), @entity34830  ( @entity34830 ) and @entity2204 ( @entity2204 ) occurs in these cells. Invasive, migratory and wound  -healing activities were observed in MDA  -MB  -231 and MCF  -10A cells following treatment with recombinant @entity1 @entity2159 , @entity34830 and @entity2204 proteins. Additionally, tube  -formation activity was assessed in @entity2159  -, @entity34830  - and @entity2204  -treated @entity1 umbilical vein endothelial cells (HUVECs). We found that @entity2159 , @entity34830 and @entity2204 affected cell motility and tube  -formation activity. Since @entity2159 markedly affected cell motility, we examined the effect of senescent conditioned media containing neutralizing @entity2159 antibodies on @entity4222 and wound  -healing activity. Our results demonstrated that IR  -induced senescent @entity5 cells influence the @entity5 microenvironment by increasing the production of cytokines, such as @entity2159 , @entity34830 and @entity2204 . Furthermore, these data suggest that @entity2159 is likely a promising target capable of reducing the deleterious effects on the @entity5 microenvironment during radiation therapy.
