Fluorescent Proteins as Visible In Vivo Sensors - Progress in Molecular Biology and Translational Science - page 391

Figure 10.2 Non-invasive, subcellular imaging of dual-color mouse mammary cancer
cells and GFP stromal cells in the live GFP-nude mouse. Dual-color mouse mammary
tumor (MMT) cells were injected in the footpad of GFP transgenic nude mice. Numerous
dual-color spindle-shaped MMT cells interacted with GFP-expressing host cells. Well-
developed tumor blood vessels and real-time blood flowwere visualized by noninvasive
imaging (arrows). Bar: 20 m m. 19
The ability to image nuclear-cytoplasmic dynamics in vivo is a major ad-
vance in our ability to understand the proliferation, quiescence, dormancy,
trafficking, and death of cancer cells in the living animal. With this powerful
technology, we will be able to visualize in vivo the most fundamental prop-
erties of cancer, including the reversible transition between cancer cell pro-
liferation and quiescence, how prolonged quiescence may lead to dormancy,
the dynamics of cell death, and the nuclear-cytoplasmic dynamics of cancer
cell spread. Most importantly, we will have an opportunity to visualize, in
real time, in the live animal the activity of novel drugs on these processes as
well as how drugs induce cell death at the subcellular level. With this tech-
nology, we can expect to discover new classes of drugs for cancer.
3. LIGHTING UP THE TUMOR STROMA
WITH FLUORESCENT PROTEINS
3.1. Imaging the recruitment of cancer-associated
fibroblasts by liver-metastatic colon cancer
The TME is critical for tumor growth and progression. In order to image
the TME, a GFP-expressing mouse was used as the host that expressed
GFP in all organs but not the parenchymal cells of the liver. Noncolored
HCT-116 human colon cancer cells were injected into the spleen of GFP-
nude mice, which led to the formation of experimental liver metastasis.