This study established and characterized low-metastatic revertant and parental clones of a highly metastatic human lung cancer cell line, NCI-H460-LNM35 (hereafter referred to as LNM35). Expression-profiling analysis revealed that up-regulation of various proinflammatory cytokines and angiogenic chemotactic chemokines was present in LNM35. Further, while COX-2 itself is known to be inducible in inflammation, COX-2 expression levels correlated well with the capabilities of these clones for not only in vitro motility and invasion but also in vivo metastasis, and COX-2 inhibitors were shown for the first time to reduce lung cancer metastasis in vivo. These findings suggest that lung cancer cells may mimic inflammatory cells in the process of metastasis.