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Cancer Biology, Immunology, Cytokines |
B Activity Correlates with Growth, Angiogenesis, and Metastasis of Human Melanoma Cells in Nude Mice1
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
The
purpose of this study was to determine the role of nuclear factor
(NF)-
B/relA activity in the induction of angiogenesis and production
of metastasis by human melanoma cells. Highly metastatic melanoma
variant cells expressed high levels of constitutive NF-B activity.
Transfection of highly metastatic human melanoma variant cells with a
dominant-negative mutant inhibitor of nuclear factor-B
(Iß) expression vector (IßM) decreased the level of
constitutive NF-B activity, inhibited s.c. tumor growth, and
prevented lung metastasis in nude mice. Furthermore, the slow-growing
s.c. tumors formed by the IBM-transfected cells exhibited a
decrease in microvessel density (angiogenesis), which correlated with a
decrease in the level of interleukin-8 expression. Collectively, these
results demonstrate that NF-B/relA activity significantly
contributes to tumorigenicity, angiogenesis, and metastasis of human
melanoma cells implanted in nude mice.
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