Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells.
The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high-frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. The expression levels of genes associated with cell cycle progression and DNA replication were remarkably reduced in the IRSL ECs. Additionally, the in vitro invasion and migration activities of these cells through Matrigel were significantly suppressed. We also found that confluent ECs exhibited a high-frequency IRSL phenotype when they were replated immediately after irradiation, whereas incubation in plateau-phase conditions reduced the induction of this phenotype and enhanced colony formation. The kinetics of DNA double-strand break repair, which showed a faster time course in confluent ECs than in growing ECs, may contribute to the protective mechanism associated with the IRSL phenotype. These results imply that the IRSL phenotype may be important for determining the angiogenic activity of ECs following irradiation. The present study should contribute to the understanding of the effects of IR on tumor angiogenesis.
Oral Radiation Oncology, Department of Oral Restitution, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Kaori
K
Igarashi
Ippei
I
Sakimoto
Keiko
K
Kataoka
Keisuke
K
Ohta
Masahiko
M
Miura
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism; D004260:DNA Repair / Q000528:radiation effects; D042783:Endothelial Cells / Q000502:physiology / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D014471:Umbilical Veins / Q000166:cytology
D004247:DNA