Abstract
e13577 Background: Dormant cancer cells are a significant problem in clinical cancer as they are usually chemoresistant and can give rise to recurrence years after treatment. Methods: Dormant cancer cells were identified with a fluorescence ubiquitination cell cycle indicator (FUCCI) and confocal microscopy. FUCCI-expressing xenografts were established from MKN45 gastric cancer cells. Results: Within 7 days after implantation in nude mice, FUCCI-expressing tumors contained a mixture of cancer cells in G0/G1 and S/G2/M phases. Cancer cells in G0/G1 phase survived and become dormant after treatment with cytotoxic agents. As the tumors grew, proliferating cells were only found at the surface. Chemotherapy killed only the 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 green fluorescent protein (GFP) transgenic mice that have GFP-expressing nascent tumor vessels. Chemotherapy-treated tumors had much more and deeper tumor vessels than control tumors. Conclusions: These results suggest that dormant cancer cells may protect themselves by inducing angiogenesis.
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