ADAM9 promotes lung cancer progression through vascular remodeling by VEGFA, ANGPT2, and PLAT
Journal
Scientific Reports
Journal Volume
7
Journal Issue
1
Date Issued
2017
Author(s)
Lin C.-Y.
Cho C.-F.
Bai S.-T.
Liu J.-P.
Kuo T.-T.
Wang L.-J.
Lin Y.-S.
Lin C.-C.
Hsieh C.-Y.
Chu C.-N.
Cheng D.-C.
Sher Y.-P.
Abstract
Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT. ? 2017 The Author(s).
SDGs
Other Subjects
ADAM protein; ADAM9 protein, human; angiopoietin 2; ANGPT2 protein, human; membrane protein; PLAT protein, human; tissue plasminogen activator; vasculotropin A; A-549 cell line; animal; brain tumor; C57BL mouse; cell culture; cell line; gene expression profiling; gene expression regulation; gene knockout; genetics; human; lung tumor; metabolism; neovascularization (pathology); pathology; procedures; secondary; tumor cell line; vascular remodeling; A549 Cells; ADAM Proteins; Angiopoietin-2; Animals; Brain Neoplasms; Cell Line; Cell Line, Tumor; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Humans; Lung Neoplasms; Membrane Proteins; Mice, Inbred C57BL; Neovascularization, Pathologic; Tissue Plasminogen Activator; Vascular Endothelial Growth Factor A; Vascular Remodeling
Publisher
Nature Publishing Group
Type
journal article