The difference of angiogenesis in human lung adenocarcinoma cell lines with different metastatic potency.
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.
Zou
Datong
D
Fourth Department of Internal Medicine, Nippon Medical School. zoudatong@hotmail.com
Shibuya
Masahiko
M
Shinoda
Kinya
K
Hibino
Suguru
S
Matsuda
Kuniko
K
Takenaka
Kiyoshi
K
Gemma
Akihiko
A
Kudoh
Shoji
S
D000230:Adenocarcinoma / Q000098:blood supply* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2