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ABSTRACT: We have developed mouse models of
metastatic cancer with genetically fluorescent tumors that can be imaged
in fresh tissue, in situ, as
well as externally. To
achieve this capability, we have transduced the green fluorescent
protein (GFP) gene, cloned from the bioluminescent jellyfish Aequorea victoria, into a series of human and rodent cancer cell
lines that were selected in vitro
to stably express GFP in vivo
after transplantation to metastatic rodent models. Techniques were also
developed for transduction of tumors by GFP in
vivo. With this
fluorescent tool, we detected and visualized for the first time tumors
and metastasis in fresh viable tissue or in situ in host organs down to
the single cell level. GFP tumors on the colon, prostate, breast, brain, liver,
lymph nodes, lung, pancreas, bone and other organs can also be
visualized externally, transcutaneously by quantitative whole-body
fluorescence optical imaging. Real-time
tumor and metastatic growth and angiogenesis and inhibition by
representative drugs can be imaged and quantified for rapid anti-tumor,
anti-metastatic and anti-angiogenesis drug screening.
The GFP-transfected tumor cells enabled a fundamental advance in
the visualization of tumor growth and metastasis in real time in
vivo. -------------------------------------------
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