Tumor metastasis and the reciprocal regulation of prometastatic and antimetastatic factors by nuclear factor κB

To investigate the role of the transcription factor nuclear factor κB (NFκB) in tumor metastasis, we generated a murine lung alveolar carcinoma cell line (Line 1) defective in NFκB-signaling by retroviral delivery of a dominant negative inhibitor of NFκB. The NFκB 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. NFκB 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 NFκB 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.