We investigated the ability of angiogenesis in PC9/F9 cells (from a highly metastatic human lung adenocarcinoma cell line) as compared with PC9 cells (from a low metastatic human lung adenocarcinoma cell line). In vivo tumor growth assay using BALB/c nude mice (7 mice/group), showed that the tumor volume of PC9/F9 cells on day 35 (230.7+/-31.3 mm(3)) was significantly larger than that of PC9 cells (90.9+/-24.7 mm(3)) (p<0.001). However, there was no significant difference between PC9/F9 cells and PC9 cells in an in vitro growth assay. In a dorsal air sac assay (DAS assay) using ICR mice (3 mice/group), PC9/F9 cells (4.7+/-1.2 vessels) showed stronger neovascurizationin in compared with PC9 cells (0.3+/-0.4 vessels) (p<0.05). In an enzyme linked immunosorbent assay (ELISA) and Western blotting analysis there were no significant differences between PC9/F9 cells and PC9 cells in the protein expression of vascular endothelial growth factor (VEGF). There was no significant difference between the gene expression levels of PC9/F9 cells and PC9 cells on cDNA array analysis. Matrix metalloproteinase-2 (MMP-2) activity in PC9/F9 cells was remarkably stronger than that of PC9 cells in Gelatin Zymography. From these results, we considered that of the increased metastasis of PC9/F9 cells might be induced by augmented angiogenesis. Furthermore, we speculated that the augmented angiogenesis of the highly metastatic PC9/F9 cell line might be induced by increased MMP-2 activity.