Stromal cells are essential for
tumor growth. Stromal cells interact with
cancer cells during
tumor growth and progression. We report here the development of a tri-color imageable mouse model to visualize the interaction between host cells and
cancer cells. To observe subcellular
cancer cell dynamics in vivo, HT-1080 human
fibrosarcoma cells were labeled in the nucleus with
histone H2B-green fluorescent
protein (GFP) and with retroviral
red fluorescent protein (RFP) in the cytoplasm. HT-1080-GFP-RFP cells were sprinkled over a skin-flap in transgenic GFP immunocompetent mice. After 24 h, the mice were imaged with an Olympus IV100
laser scanning microscope. HT-1080-GFP-RFP cells were visualized surrounded by host-derived lymphocytes and macrophages both expressing GFP. It was possible to observe host GFP macrophages contacting, engulfing, and digesting dual-color HT-1080-GFP-RFP cells in real time. The dual-color
cancer cells were readily visible after being engulfed in the GFP macrophages. Other
cancer cells were visualized being killed by lymphocytes. The results of this study show that differentially labeling cells with spectrally-distinct fluorescent
protein can allow subcellular-resolution imaging of cell-cell interactions between host and
cancer cells.