Abstract PR14: Real-time in-vivo image-guided cell-cycle perturbation to increase tumor chemosensitivity

Tumor heterogeneity has been recognized as a major reason for anticancer drug resistance and therapy failure in solid cancers. Therefore, we simply categorized the tumor heterogeneity as cycling and quiescent cancer cells. A multi-color genetic reporter system has been previously-developed termed fluorescence ubiquitination cell cycle indicator (FUCCI) (Cell 2008; 132:487-98) whereby cycling cells fluorescence yellow/green and quiescent cells fluoresce red. We demonstrated the monitoring of real-time spatiotemporal cell cycle dynamics of cancer cells throughout a live tumor intravitally using a FUCCI system. According to cell cycle distribution, we defined three in vivo tumor models; an early stage nascent tumor consists of proliferating cancer cells, a late-stage established tumor consists on proliferating cancer cells at the surface area and quiescent cancer cells at the center area, and a dormant tumor consists of almost quiescent cancer cells without changing the cell cycle and the size for more than two months. Longitudinal intravital real-time imaging in living mice also demonstrated that cytotoxic agents killed only cycling cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of a late-stage established tumor and a dormant tumor. Moreover, resistant quiescent cancer cells restarted cycling after the cessation of chemotherapy. We have utilized FUCCI in vivo intravital real-time imaging to first determine ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Getting out of Cycle: G0 and Senescence: Oral Presentations - Proffered Abstracts Source Type: research