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

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

doi:10.1016/j.ejcb.2011.03.005

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

Eur J Cell Biol. 2011 Aug;90(8):642-8. doi: 10.1016/j.ejcb.2011.03.005. Epub 2011 May 26.

Authors

Yingyi Wang¹, 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

Affiliation

¹ Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.

PMID: 21616556
DOI: 10.1016/j.ejcb.2011.03.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Integrin alphaVbeta3 / immunology
Integrin alphaVbeta3 / metabolism
Membrane Proteins / pharmacology
Morpholines / pharmacology
Neovascularization, Physiologic*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type III / antagonists & inhibitors
Nitric Oxide Synthase Type III / metabolism
Osteopontin / genetics
Osteopontin / 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
Stem Cells / metabolism*
Vascular Endothelial Growth Factors / biosynthesis

Substances

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