Abstract 1758: Cancer cell location in tumor determines cell cycle position and dormancy.

Abstract

Abstract The phase of the cell cycle can determine whether a cancer cell can respond to most drugs. The fluorescence ubiquitination cell cycle indicator (FUCCI) was used to image the cell cycle phase within tumors. In nascent tumors in nude mice, approximately 30% of the cells in the center of the tumor were in G0/G1 and 70% in S/G2/M. In contrast, approximately 90% of cancer cells in the center of an established tumor were in G0/G1 phase. Similarly, approximately 75% of cancer cells far from (>100 μm) tumor vessels were in G0/G1. Although 60-70% of cancer cells near the surface of an established tumor (< 100 μm) or near blood vessels were in S/G2/M, these cells are a small minority of an established tumor. Moreover, tumors that are stable in size for more than six months in nude mice consisted of mostly G0/G1 cells, suggesting they are dormant. The results presented here have profound implications for cancer therapy, since most drugs currently in use target cells in S/G2/M, which are a minor fraction in an established tumor. With the developments reported here, drugs that target non-dividing and dormant cancer cells can be readily identified. Citation Format: Shuya Yano, Yasunori Tome, Michelle Digman, Masashi Momiyama, Atsushi Suetsugu, Enrico Gratton, Robert M. Hoffman. Cancer cell location in tumor determines cell cycle position and dormancy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1758. doi:10.1158/1538-7445.AM2013-1758