Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells.

Abstract

Angiogenesis, a hallmark of tumor growth, is regulated by various angiogenic factors. Recent studies have shown that osteopontin (OPN) is a secreted, integrin-binding protein that contributes to glioma progression. However, its effect on the angiogenesis of gliomas is not fully understood. To elucidate the role of OPN in the process of glioma angiogenesis, endothelial progenitor cells (EPCs) were treated with conditioned media of human glioma SHG44 cells overexpressing OPN. Here, we identified that OPN secreted by glioma cells accelerated EPCs angiogenesis in vitro, including proliferation, migration, and tube formation. OPN also induced the activation of AKT and endothelial nitric oxide synthase (eNOS) and increased NO production without affecting the expression of VEGF, VEGFR-1, or VEGFR-2. Moreover, the avβ3 antibody, the PI3-K inhibitor LY294002 and the eNOS inhibitor NMA suppressed the OPN-mediated increase in NO production and angiogenesis in EPCs. Taken together, these results demonstrate that OPN directly stimulates angiogenesis via the avβ3/PI3-K/AKT/eNOS/NO signaling pathway and may play an important role in tumorigenesis by enhancing angiogenesis in gliomas.

• Authors: Yingyi Wang, Wei Yan, Xiaoming Lu, Chunfa Qian, Junxia Zhang, Ping Li, Lei Shi, Peng Zhao, Zhen Fu, Peiyu Pu, Chunshen Kang, Tao Jiang, Ning Liu, Yongping You
• Journal: European journal of cell biology (Eur J Cell Biol) Vol. 90 Issue 8 Pg. 642-8 (Aug 2011) ISSN: 1618-1298 [Electronic] Germany
• PMID: 21616556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier GmbH. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• BAMBI protein, human
• Chromones
• Enzyme Inhibitors
• Integrin alphaVbeta3
• Membrane Proteins
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Vascular Endothelial Growth Factors
• Osteopontin
• Nitric Oxide
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Nitric Oxide Synthase Type III
• Receptors, Vascular Endothelial Growth Factor
• Proto-Oncogene Proteins c-akt

Topics

• Antibodies, Monoclonal (pharmacology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chromones (pharmacology)
• Endothelial Cells (cytology)
• Enzyme Inhibitors (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression
• Glioma (metabolism)
• Humans
• Integrin alphaVbeta3 (antagonists & inhibitors, immunology, metabolism)
• Membrane Proteins (pharmacology)
• Morpholines (pharmacology)
• Neovascularization, Physiologic
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type III (antagonists & inhibitors, metabolism)
• Osteopontin (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, Vascular Endothelial Growth Factor (biosynthesis)
• Signal Transduction
• Stem Cells (cytology, metabolism)
• Vascular Endothelial Growth Factors (biosynthesis)