Glioma cells enhance endothelial progenitor cell angiogenesis via VEGFR-2, not VEGFR-1.

Although potential contribution of endothelial progenitor cells (EPCs) to angiogenesis in glioma has been proposed, the molecular mechanisms of EPCs recruitment to vasculature have not been fully elucidated. Here, we show that the supernatant from glioma cells promotes EPCs angiogenesis via VEGFR-2, not VEGFR-1. Moreover, VEGFR-2 siRNA inhibits VEGFR-2 expression in EPCs, tube formation on matrigel and cell migration. MMP-9 activity and expression and the Akt and ERK phosphorylations are decreased by VEGFR-2 siRNA. Thus, these results indicate that glioma cells enhance EPC angiogenesis via VEGFR-2, not VEGFR-1, mediated by the MMP-9, Akt and ERK signal pathways.

[1]  K. Park,et al.  Akt Is a Key Modulator of Endothelial Progenitor Cell Trafficking in Ischemic Muscle , 2007, Stem cells.

[2]  D. Jeoung,et al.  A Splice Variant of CD99 Increases Motility and MMP-9 Expression of Human Breast Cancer Cells through the AKT-, ERK-, and JNK-dependent AP-1 Activation Signaling Pathways* , 2006, Journal of Biological Chemistry.

[3]  Tom T. Chen,et al.  Vascular Endothelial Growth Factor Receptor 2 Plays a Role in the Activation of Aortic Endothelial Cells by Oxidized Phospholipids , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[4]  M. Shibuya Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. , 2006, Journal of biochemistry and molecular biology.

[5]  A. Parker,et al.  Delivery of RNA Interference , 2006, Cell cycle.

[6]  Jiyoung Kim,et al.  Human lactoferrin upregulates expression of KDR/Flk‐1 and stimulates VEGF‐A‐mediated endothelial cell proliferation and migration , 2006, FEBS letters.

[7]  Yan Zeng,et al.  Diallyl Trisulfide Inhibits Angiogenic Features of Human Umbilical Vein Endothelial Cells by Causing Akt Inactivation and Down-Regulation of VEGF and VEGF-R2 , 2006, Nutrition and cancer.

[8]  A. Aigner Gene silencing through RNA interference (RNAi) in vivo: strategies based on the direct application of siRNAs. , 2006, Journal of biotechnology.

[9]  D. Ribatti The involvement of endothelial progenitor cells in tumor angiogenesis , 2004, Journal of cellular and molecular medicine.

[10]  X. Moore,et al.  Endothelial progenitor cells’ ‘homing’ specificity to brain tumors , 2004, Gene Therapy.

[11]  Hyun-Jae Kang,et al.  Characterization of Two Types of Endothelial Progenitor Cells and Their Different Contributions to Neovasculogenesis , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[12]  I. Hwang,et al.  Localization of VEGFR-2 and PLD2 in endothelial caveolae is involved in VEGF-induced phosphorylation of MEK and ERK. , 2004, American journal of physiology. Heart and circulatory physiology.

[13]  H. Fine,et al.  Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors , 2003, Gene Therapy.

[14]  Michelle L. Varney,et al.  IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis1 , 2003, The Journal of Immunology.

[15]  Jiankun Cui,et al.  S-Nitrosylation of Matrix Metalloproteinases: Signaling Pathway to Neuronal Cell Death , 2002, Science.

[16]  I. Shiojima,et al.  Role of Akt Signaling in Vascular Homeostasis and Angiogenesis , 2002, Circulation research.

[17]  G. Mcmahon,et al.  Inhibition of vascular endothelial growth factor-associated tyrosine kinase activity with SU5416 blocks sprouting in the microvascular endothelial cell spheroid model of angiogenesis. , 2002, Microvascular research.

[18]  S. Fichtlscherer,et al.  Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease , 2001, Circulation research.

[19]  Thiennu H. Vu,et al.  Matrix Metalloproteinase 9 and Vascular Endothelial Growth Factor Are Essential for Osteoclast Recruitment into Developing Long Bones , 2000, The Journal of cell biology.

[20]  Shigeyoshi Itohara,et al.  Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis , 2000, Nature Cell Biology.

[21]  Thiennu H. Vu,et al.  Matrix metalloproteinases: effectors of development and normal physiology. , 2000, Genes & development.

[22]  K. Pantel,et al.  In vitro differentiation of endothelial cells from AC133-positive progenitor cells , 2000 .

[23]  L. Mayo,et al.  Tumor Necrosis Factor Employs a Protein-tyrosine Phosphatase to Inhibit Activation of KDR and Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation* , 2000, The Journal of Biological Chemistry.

[24]  J. Isner,et al.  Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Isner,et al.  Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. , 1999, Circulation research.

[26]  J. Isner,et al.  VEGF contributes to postnatal neovascularization by mobilizing bone marrow‐derived endothelial progenitor cells , 1999, The EMBO journal.

[27]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[28]  J. Rossant,et al.  Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium , 1995, Nature.