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Clinical Cancer Research Vol. 5, 3549-3559, November 1999
© 1999 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Genetically Fluorescent Melanoma Bone and Organ Metastasis Models1

Meng Yang, Ping Jiang, Zili An, Eugene Baranov, Lingna Li, Satoshi Hasegawa, Maraya Al-Tuwaijri, Takashi Chishima, Hiroshi Shimada, A. R. Moossa and Robert M. Hoffman2

AntiCancer, Inc., San Diego, California 92111 [M. Y., P. J., Z. A., E. B., L. L., S. H., M. A-T., R. M. H.]; Department of Surgery, University of California, San Diego, California 92103-8220 [M. Y., S. H., M. A-T., A. R. M., R. M. H.]; and Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan 236 [M. Y., S. H., T. C., H. S.]

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 µg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.




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Copyright © 1999 by the American Association for Cancer Research.