Abstract
This study was conducted to investigate the biological role of periostin in gastric cancer (GC) under hypoxia. Western blot analysis revealed that along with an upregulation of hypoxia-inducible factor-1alpha, there was a time-dependent induction of periostin in MKN-45 cells under hypoxia (2% O2 ), increasing by eightfold as compared to normoxic cells. Pretreatment with 30 µM PD98059, an inhibitor of ERK1/2, significantly reduced hypoxia-stimulated periostin expression (P < 0.01). Periostin knockdown in MKN-45 cells was achieved by specific small interfering RNA (siRNA). The conditioned medium from periostin siRNA-transfected MKN-45 cells induced significantly less (P < 0.01) endothelial tube formation than control siRNA-transfected cells. Additionally, periostin silencing markedly decreased the mRNA expression and secretion of vascular endothelial growth factor (VEGF) in hypoxic MKN-45 cells. Thus, our data suggest that periostin is a hypoxia-response gene and mediates a cross talk between GC and endothelial cells under hypoxia, partially through regulation of the VEGF expression.
Keywords:
Angiogenesis; Gastric Cancer; Hypoxia; Periostin; Vascular Endothelial Growth Factor.
© 2013 Wiley Periodicals, Inc.
MeSH terms
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Communication / drug effects
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Cell Communication / genetics
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Cell Hypoxia / genetics
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Cell Line, Tumor
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Coculture Techniques
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Flavonoids / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Gene Knockdown Techniques
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Human Umbilical Vein Endothelial Cells
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Humans
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / mortality
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Neovascularization, Pathologic / pathology
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Protein Kinase Inhibitors / pharmacology
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Stomach Neoplasms / genetics
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Vascular Endothelial Growth Factor A / biosynthesis*
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Vascular Endothelial Growth Factor A / genetics
Substances
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Cell Adhesion Molecules
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Flavonoids
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Neoplasm Proteins
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POSTN protein, human
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Protein Kinase Inhibitors
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one