期刊
CELL CYCLE
卷 16, 期 5, 页码 406-414出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2016.1220461
关键词
angiogenesis; cell cycle; chemotherapy; decoy; FUCCI; imaging; resistance; quiescence
类别
资金
- Ministry of Health, Labor, and Welfare, Japan [10103827, 13801426, 14525167]
- Ministry of Education, Culture, Sports, Science and Technology, Japan [25293283]
- Grants-in-Aid for Scientific Research [25293283] Funding Source: KAKEN
We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G(2) phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression.
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