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ID 110451
タイトルヨミ
ヒト ハイガン サイボウ ニヨル ガンセイ キョウスイ ケイセイ ニオケル VEGF Vascular Endothelial Growth Factor ノ イギ
タイトル別表記
Role of vascular endothelial growth factor in the formation of malignant pleural effusion
著者
矢野, 聖二 徳島大学医学部第三内科
軒原, 浩 徳島大学医学部第三内科 徳島大学 教育研究者総覧
三木, 豊和 徳島大学医学部第三内科
Fidler, Isaiah J. MD アンダーソン癌センター癌生物学教室
キーワード
VEGF
pleural effusion
angiogenesis
資料タイプ
その他
抄録
The purpose of this study was to determine the molecular mechanisms that regulate the pathogenesis of malignant pleural effusion (PE) associated with advanced stage human non-small cell lung cancer. Intravenous injection of human PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells into nude mice yielded numerous lung lesions. PC14 PE6 lung lesions invaded the pleura and produced PE containing a high level of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), resulting in vascular hyperpermeability in the thoracic cavity. Lung lesions produced by H226 cells were confined to the lung parenchyma and did not induce PE. The expression of VEGF/VPF mRNA and protein by the cell lines directly correlated with PE formation. Transfection of H226 cells with either sense-VEGF 165 or sense-VEGF 121 genes did not increase cell invasion into the pleura nor induce formation of PE. However, the injection of the VEGF/ VPF-transfected H226 cells into the pleural space resulted in induction of vascular hyperpermeability and PE, indicating that the production of malignant PE requires tumor cells to invade the pleura and express high levels of VEGF/VPF. Therefore, targeting these steps may control malignant PE in lung cancer patients. PTK787, an inhibitor of VEGF/VPF receptor tyrosine kinase phosphorylation, does not affect the in vitro proliferation of PC14PE6 cells. Oral feeding with PTK787 significantly reduced the formation of PE, but not the number of lung lesions of PC14PE6 cells. Furthermore, treatment with PTK787 significantly suppressed vascular hyperpermeability of PE-bearing mice, suggesting that PTK787 reduced PE formation mainly by inhibition of vascular permeability. Therefore, the VEGF/VPF receptor tyrosine kinase inhibitor PTK787 could be useful clinically for the control of malignant PE in lung cancer patients.
掲載誌名
四国医学雑誌
ISSN
00373699
cat書誌ID
AN00102041
出版者
徳島医学会
56
3
開始ページ
109
終了ページ
110
並び順
109
発行日
2000-06-25
フルテキストファイル
言語
jpn
著者版フラグ
出版社版
部局
病院
医学系