がん間質中の老化細胞の同定と性状解析

抄録

Cellular senescence is triggered by diverse genotoxic stimuli. An important hallmark of senescent cells is its inability to proliferate in response to physiological mitotic stimuli, which can prevent tumorigenesis. Another is the appearance of Senescence-associated secretory phenotypes (SASP), such as robust secretion of numerous cytokines, which may cause deleterious effects on tissue microenvironment. Recent studies indicate that the elimination of senescent cells accumulated in the body during aging ameliorates age-related diseases including cancer, thus promoting the healthy lifespan. Therefore, cellular senescence likely plays both positive and negative roles in cancer. Recently, we generated a p16^Ink4a-Cre^ERT2-tdTomato mouse to analyze the in vivo characteristics of senescent cells. Our new mouse model and single-cell analyses suggest that in vivo senescent cells exhibited heterogeneous senescence-associated phenotypes during aging. Currently, we are trying to apply this approach to some cancer models, and we found that cancer-related senescent cells also are composed of several cell types and have various characteristics. Further analysis will provide a molecular basis for context-dependent effects of cellular senescence in cancer.