Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging
| Autor: | Hiroshi Tazawa, Toshiyoshi Fujiwara, Shuya Yano, Robert M. Hoffman, Shunsuke Kagawa, Kiyoto Takehara, Hiroyuki Kishimoto, Yasuo Urata |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tumor angiogenesis Angiogenesis medicine.medical_treatment Mice Nude Antineoplastic Agents Fluorescence Green fluorescent protein 03 medical and health sciences Imaging Three-Dimensional Ubiquitin In vivo Computer Systems Cell Line Tumor Neoplasms medicine Animals Humans Molecular Biology Chemotherapy biology Neovascularization Pathologic Cell Cycle Ubiquitination Cell Biology Cell cycle Cell biology 030104 developmental biology Drug Resistance Neoplasm Cancer cell biology.protein Blood Vessels Developmental Biology Reports |
| Popis: | 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/G2 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. |
| Databáze: | OpenAIRE |
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