Orthotopic Transplant Mouse Models with Green Fluorescent Protein-expressing Cancer Cells to Visualize Metastasis and Angiogenesis |
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Authors: | Robert M Hoffman |
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Institution: | (1) AntiCancer, Inc., San Diego, CA, USA;(2) Department of Surgery, UCSD Medical Center, San Diego, CA, USA |
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Abstract: | There have been major efforts in metastasis research in recent years, especially on the role of angiogenesis in the metastatic
process. Much of the information in this area has been obtained from model systems that are not representative of clinical
cancer. The technique of surgical orthotopic implantation (SOI) has allowed the development of clinically relevant metastatic
models of human cancer in immunodeficient rodents such as the nude and SCID mouse. In order to allow direct visualization
of the metastatic process, we took advantage of the green fluorescent protein (GFP) of the jellyfish, Aequorea victoria. A
series of cancer cell lines have been stably transfected with vectors containing humanized GFP cDNA. To utilize GFP expression
for metastasis studies, fragments of subcutaneously growing tumor, which were comprised of GFP-expressing cells, were implanted
by SOI in nude mice. Subsequent metastases were visualized in systemic organs by GFP fluorescence in the lung, liver, bones,
brain and other organs down to the single-cell level. With this fluorescent tool, we detected and visualized for the first
time tumor cells at the microscopic level in fresh viable tissue in their normal host organs even in the live animal. Angiogenesis
is readily visualized in the transplanted GFP-expressing tumors in real time in situ in the live animal using simple laparotomy
and fluorescent techniques. The results with the GFP-transfected tumor cells, combined with the use of SOI, demonstrate a
fundamental advance to visualize and study cancer metastasis and the role of angiogenesis and other factors in the metastatic
process.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | metastasis orthotopic intact tissue implantation GFP nude mice |
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