Nuclear factor-kappaB activity correlates with growth, angiogenesis, and metastasis of human melanoma cells in nude mice.
The purpose of this study was to determine the role of nuclear factor (NF)-kappaB/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-kappaB activity. Transfection of highly metastatic human melanoma variant cells with a dominant-negative mutant inhibitor of nuclear factor-kappaB alpha (Ikappabeta alpha) expression vector (Ikappabeta alphaM) decreased the level of constitutive NF-kappaB activity, inhibited s.c. tumor growth, and prevented lung metastasis in nude mice. Furthermore, the slow-growing s.c. tumors formed by the IkappaB alphaM-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-kappaB/reLA activity significantly contributes to tumorigenicity, angiogenesis, and metastasis of human melanoma cells implanted in nude mice.
Huang
S
S
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
DeGuzman
A
A
Bucana
C D
CD
Fidler
I J
IJ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1