Abstract

Abstract Dormant cancer cells were visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). FUCCI-expressing xenografts were established from MKN45 gastric cancer cells. Within 7 days after inoculation, FUCCI-expressing nascent tumors contained a mixture of cancer cells in G0/G1 phase and in S/G2/M phases. Nascent tumors treated with cyto-toxic agents showed that cancer cells in G0/G1 phase can survive and become dormant. As tumors grew, the proliferating area was only at the surface and the dormant area predominated. Chemotherapy killed only the minority population of proliferating cancer cells at the surface and had little effect on the majority of dormant cancer cells in the tumor center. Furthermore, we investigated tumor chemoresistance using nestin-driven GFP transgenic mice that have GFP-expressing nascent tumor vessels. Chemotherapy-treated tumors had much more and deeper tumor vessels than control tumors, suggesting that dormant cancer cells may protect themselves by inducing tumor vessels. This report suggests that dormant cancer cells play a large role in drug resistance. Citation Format: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Toshiyoshi Fujiwara, Robert M. Hoffman. Dormant cancer cells are resistant to conventional therapies and induce tumor vessels after chemotherapy. [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 1754. doi:10.1158/1538-7445.AM2013-1754

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