Governing step of metastasis visualized in vitro
- Takashi Chishima*,†,
- Meng Yang*,†,‡,
- Yohei Miyagi§,
- Lingna Li‡,
- Yuying Tan‡,
- Eugene Baranov‡,
- Hiroshi Shimada*,
- A. Rahim Moossa†,
- Sheldon Penman‡,¶, and
- Robert M. Hoffman†,‡,‖
- Departments of *Surgery and §Pathology, Yokohama City University School of Medicine, Yokohama 231, Japan; †Department of Surgery, University of California, 200 W. Arbor Drive, San Diego, CA 92103-8220; ‡AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111; and ¶Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg. 68, Room 232, Cambridge, MA 02139
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Contributed by Sheldon Penman
Abstract
Metastasis is the ultimate life-threatening stage of cancer. The lack of accurate model systems thwarted studies of the metastatic cell’s basic biology. To follow continuously the succeeding stages of metastatic colony growth, we heritably labeled cells from the human lung adenocarcinoma cell line ANIP 973 with green fluorescent protein (GFP) by transfection with GFP cDNA. Labeled cells were then injected intravenously into nude mice, where, by 7 days, they formed brilliantly fluorescing metastatic colonies on mouse lung [Chishima, T., Miyagi, Y., Wang, X., Yang, M., Tan, Y., Shimada, H., Moossa, A. R. & Hoffman, R. M. (1997) Clin. Exp. Metastasis 15, 547–552]. The seeded lung tissue was then excised and incubated in the three-dimensional sponge-gel-matrix-supported histoculture that maintained the critical features of progressive in vivo tumor colonization while allowing continuous access for measurement and manipulation. Tumor progression was continuously visualized by GFP fluorescence in the same individual cultures over a 52-day period, during which the tumors spread throughout the lung. Histoculture tumor colonization was selective for lung cancer cells to grow on lung tissue, because no growth occurred on histocultured mouse liver tissue, which was also observed in vivo. The ability to support selective organ colonization in histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis [Kuo, T.-H., Kubota, T., Watanbe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A. R., Penman, S. & Hoffman, R. M. (1995) Proc. Natl. Acad. Sci. USA 92, 12085–12089]. The results presented here provide significant, new opportunities to understand and to develop treatments that prevent and possibly reverse metastasis.
Footnotes
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↵ ‖ To whom reprint requests should be addressed at: AntiCancer, Inc., San Diego, CA 92111. e-mail: all{at}anticancer.com.
- ABBREVIATIONS:
- GFP,
- green fluorescent protein;
- MTX,
- methotrexate
- Copyright © 1997, The National Academy of Sciences of the USA
