Tumor metastasis and the reciprocal regulation of prometastatic and antimetastatic factors by nuclear factor kappaB.
Cancer Res
; 60(23): 6557-62, 2000 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-11118032
ABSTRACT
To investigate the role of the transcription factor nuclear factor kappaB (NFkappaB) in tumor metastasis, we generated a murine lung alveolar carcinoma cell line (Line 1) defective in NFkappaB-signaling by retroviral delivery of a dominant negative inhibitor of NFkappaB. The NFkappaB signal blockade resulted in the down-regulation of prometastatic matrix metalloproteinase 9, a urokinase-like plasminogen activator, and heparanase and reciprocal up-regulation of antimetastatic tissue inhibitors of matrix metalloproteinases 1 and 2 and plasminogen activator inhibitor 2. NFkappaB signal blockade did not affect tumor cell proliferation in vitro or in vivo but prevented intravasation of tumor cells in an in vivo chick chorioallantoic membrane model of metastasis as well as spontaneous metastasis in a murine model. These findings suggest that NFkappaB plays a central and specific role in the regulation of tumor metastasis and may be an important therapeutic target for development of antimetastatic cancer treatments.
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Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
FN-kappa B
/
Metástasis de la Neoplasia
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2000
Tipo del documento:
Article