ID 110451
Title Transcription
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
Title Alternative
Role of vascular endothelial growth factor in the formation of malignant pleural effusion
Author
Yano, Seiji Third Department of Internal Medicine, The University of Tokushima School of Medicine
Nokihara, Hiroshi Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory
Miki, Toyokazu Third Department of Internal Medicine, The University of Tokushima School of Medicine
Nishioka, Yasuhiko Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Fidler, Isaiah J. Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center
Sone, Saburo Third Department of Internal Medicine, The University of Tokushima School of Medicine Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
VEGF
pleural effusion
angiogenesis
Content Type
Others
Description
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.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
56
Issue
3
Start Page
109
End Page
110
Sort Key
109
Published Date
2000-06-25
FullText File
language
jpn
TextVersion
Publisher
departments
University Hospital
Medical Sciences