Journal of Nippon Medical School: Vol.71 No.3 page.181

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ArticleTitle The Difference of Angiogenesis in Human Lung Adenocarcinoma Cell Lines with Different Metastatic Potency

AuthorList Datong Zou¹, Masahiko Shibuya², Kinya Shinoda³, Suguru Hibino¹, Kuniko Matsuda¹, Kiyoshi Takenaka¹, Akihiko Gemma¹ and Shoji Kudoh¹

Affiliation ¹Fourth Department of Internal Medicine, Nippon Medical School
²Respiratory Division of Internal Medicine, Tokyo Metropolitan Komagome Hospital
³Deparment of Pulmonology, International Medical Center of Japan

Language JA

Volume 71

Issue 3

Year 2004

Page 181-189

Received August 8, 2003

Accepted February 9, 2004

Keywords human lung adenocarcinoma cell line, angiogenesis, metastasis, VEGF, MMP-2

Abstract
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 mm³) was significantly larger than that of PC9 cells (90.9±24.7 mm³) (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.

Correspondence to Datong Zou, MD, Fourth Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
zoudatong@hotmail.com

ArticleTitle	The Difference of Angiogenesis in Human Lung Adenocarcinoma Cell Lines with Different Metastatic Potency
AuthorList	Datong Zou¹, Masahiko Shibuya², Kinya Shinoda³, Suguru Hibino¹, Kuniko Matsuda¹, Kiyoshi Takenaka¹, Akihiko Gemma¹ and Shoji Kudoh¹
Affiliation	¹Fourth Department of Internal Medicine, Nippon Medical School ²Respiratory Division of Internal Medicine, Tokyo Metropolitan Komagome Hospital ³Deparment of Pulmonology, International Medical Center of Japan
Language	JA
Volume	71
Issue	3
Year	2004
Page	181-189
Received	August 8, 2003
Accepted	February 9, 2004
Keywords	human lung adenocarcinoma cell line, angiogenesis, metastasis, VEGF, MMP-2
Abstract	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 mm³) was significantly larger than that of PC9 cells (90.9±24.7 mm³) (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.
Correspondence to	Datong Zou, MD, Fourth Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan zoudatong@hotmail.com