ABSTRACT 1759(P7-3)
TUMOR ANGIOGENESIS VISUALIZED IN SITU IN LIVE ANIMALS WITH GFP-EXPRESSING HUMAN CANCER CELLS
M. Yang1, T. Chishima2, H. Shimada2, A.R. Moossa3,, R.M. Hoffman1,3. 1AntiCancer, Inc., 7917 Ostrow Street, San Diego, California 92111 U.S.A.; 2Second Dept. Of Surgery, Yokohama City Univ. School of Medicine, Yokohama, Japan; 3,Univ. of California, San Diego, Department of Surgery, San Diego, California, U.S.A.
Green fluorescent protein (GFP)-expressing cell-lines have been established in vitro that permit the detection and visualization in live tissue of primary tumors and micrometastases when they are implanted orthotopically or colonizing normal organs in histoculture1-5. Hamster and human cancer cell lines were transfected with vectors containing the humanized GFP cDNA. Stable high-level expression of GFP was maintained in the subcutaneously and orthotopically growing tumors in nude mice. Subsequent micrometastases were visualized by GFP fluorescence in live tissue of the lung, liver, brain, and other organs down to the single-cell level. The onset and progression of angiogenesis of the growing and spreading GFP tumors was visualized by injecting a fluorescent rhodamine dye to the GFP-tumor-bearing mice which lights up blood vessels including those forming in the GFP tumor cells. The data thus far acquired from multiple laparotomy observations over time in GFP-tumor-bearing mice indicate that the onset and extent of tumor angiogenesis depends on the site and type of the growing tumor in the animal. This model is ideal for the study of the role of angiogenesis in cancer and discovery of new angiogenesis and metastasis inhibitors.
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2 Chishima, T., et al., Clin & Exp Meta 15, 547-552, 1997.
3 Chishima, T., et al., Anticancer Research 17, 2377-2384, 1997.
4 Chishima, T., et al., Proc. Natl. Acad. Sci. USA 94, 11573-11576, 1997.
5 Chishima, T., et al., In Vitro Cell. Dev. Biol. 33, 745-747, 1997.