Home LiteratureArticle Details
PMID: 18205708 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles.

Journal of cellular and molecular medicine ·Vol. 11 ·No. 6 ·2007-00-00 ·Pages 1384-94

Schiera G, Proia P, Alberti C, Mineo M, Savettieri G, Di Liegro I

Abstract

We previously found that neurons are able to affect the ability of brain capillary endothelial cells to form in vitro a monolayer with properties resembling the blood-brain barrier. We then looked, by immunofluorescence and western analysis, for factors, produced by neurons, with the potential to influence growth and differentiation of endothelial cells. In the present paper, we report that neurons produce both vascular endothelial growth factor and fibroblast growth factor 2, two well-known angiogenic factors. More interestingly, we gained evidence that both factors are released by neurons, at least in part, by shedding of extracellular vesicles, that contain beta1 integrin, a membrane protein already known to be part of extracellular vesicles released by tumour cells. Shedding of extracellular vesicles by neurons was also confirmed by scanner electron microscopy.

MeSH Terms
Animals Astrocytes/cytology,drug effects,metabolism Camptothecin/pharmacology Cells, Cultured Extracellular Space/drug effects,metabolism Fibroblast Growth Factor 2/metabolism Glial Fibrillary Acidic Protein/metabolism Integrin beta1/metabolism Neurofilament Proteins/metabolism Neurons/cytology,drug effects,metabolism,ultrastructure Protein Transport/drug effects Rats Rats, Wistar Secretory Vesicles/drug effects,metabolism Vascular Endothelial Growth Factor A/metabolism
Chemicals
Glial Fibrillary Acidic Protein Integrin beta1 Neurofilament Proteins Vascular Endothelial Growth Factor A Fibroblast Growth Factor 2 Camptothecin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schiera Gabriella
Dipartimento di Scienze Biochimiche, Università degli Studi di Palermo, Palermo, Italy.
Proia Patrizia
Alberti Chiara
Mineo Marco
Savettieri Giovanni
Di Liegro Italia
References (41)
41 references, click to expand
  1. Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures.
    Brain Res. 2007 Jun 18;1154:40-9 PMID: 17498671
  2. Membrane vesicles shed by oligodendroglioma cells induce neuronal apoptosis.
    Int J Oncol. 2006 Nov;29(5):1075-85 PMID: 17016637
  3. New vascular endothelial growth factor isoform generated by internal ribosome entry site-driven CUG translation initiation.
    Mol Endocrinol. 2001 Dec;15(12):2197-210 PMID: 11731620
  4. Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity.
    J Cell Biol. 1996 Aug;134(3):757-70 PMID: 8707853
  5. Neurons and ECM regulate occludin localization in brain endothelial cells.
    Neuroreport. 2000 Apr 7;11(5):1081-4 PMID: 10790886
  6. Characterization of plasma membrane shedding from murine melanoma cells.
    Int J Cancer. 1988 Apr 15;41(4):629-35 PMID: 3356493
  7. Angiogenesis.
    J Biol Chem. 1992 Jun 5;267(16):10931-4 PMID: 1375931
  8. Functional feature of a novel model of blood brain barrier: studies on permeation of test compounds.
    J Control Release. 2001 Sep 11;76(1-2):139-47 PMID: 11532320
  9. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.
    Mol Biol Cell. 1993 Dec;4(12):1317-26 PMID: 8167412
  10. Surface membrane-associated regulation of cell assembly, differentiation, and growth.
    Blood. 1991 Jul 15;78(2):264-76 PMID: 2070064
  11. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells.
    Am J Pathol. 2002 Feb;160(2):673-80 PMID: 11839588
  12. Emission of membrane vesicles: roles in complement resistance, immunity and cancer.
    Springer Semin Immunopathol. 2005 Nov;27(3):375-87 PMID: 16189651
  13. Investigating the effect of VEGF glycosylation on glycosaminoglycan binding and protein unfolding.
    Biochem Biophys Res Commun. 2006 Feb 17;340(3):836-9 PMID: 16386708
  14. Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells.
    Cancer Res. 1998 Oct 1;58(19):4468-74 PMID: 9766680
  15. VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS?
    Trends Mol Med. 2004 Jun;10(6):275-82 PMID: 15177192
  16. Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust long-term survival and integration and suppress aberrant mossy fiber sprouting in the injured middle-aged hippocampus.
    Neurobiol Dis. 2006 Feb;21(2):276-90 PMID: 16099669
  17. Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells.
    J Biol Chem. 2003 Dec 19;278(51):51911-9 PMID: 14523006
  18. Human breast carcinoma cells cultured in the presence of serum shed membrane vesicles rich in gelatinolytic activities.
    J Submicrosc Cytol Pathol. 1994 Apr;26(2):173-80 PMID: 8019942
  19. Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells.
    Proc Natl Acad Sci U S A. 1980 Jan;77(1):399-403 PMID: 6928631
  20. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers.
    J Natl Cancer Inst. 1994 Mar 2;86(5):356-61 PMID: 7508518
  21. Sphingosine-1-phosphate: an enigmatic signalling lipid.
    Nat Rev Mol Cell Biol. 2003 May;4(5):397-407 PMID: 12728273
  22. Synergistic effects of neurons and astrocytes on the differentiation of brain capillary endothelial cells in culture.
    J Cell Mol Med. 2003 Apr-Jun;7(2):165-70 PMID: 12927055
  23. A precursor form of vascular endothelial growth factor arises by initiation from an upstream in-frame CUG codon.
    Biochem J. 2001 Oct 1;359(Pt 1):219-26 PMID: 11563986
  24. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):159-78 PMID: 15863032
  25. Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines.
    Clin Exp Metastasis. 2000;18(2):163-70 PMID: 11235992
  26. Synergistic effects of laminin and thyroid hormones on neuron polarity in culture.
    Neuroreport. 1999 Apr 26;10(6):1269-72 PMID: 10363937
  27. The biology of vascular endothelial growth factor.
    Endocr Rev. 1997 Feb;18(1):4-25 PMID: 9034784
  28. Fibroblast growth factors: at the heart of angiogenesis.
    Cell Biol Int. 1995 May;19(5):431-44 PMID: 7543787
  29. Fibroblast growth factor-2 requires glial-cell-line-derived neurotrophic factor for exerting its neuroprotective actions on glutamate-lesioned hippocampal neurons.
    Mol Cell Neurosci. 2002 Jun;20(2):181-97 PMID: 12093153
  30. The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness.
    Anticancer Res. 1998 Sep-Oct;18(5A):3433-7 PMID: 9858920
  31. Biological roles of fibroblast growth factor-2.
    Endocr Rev. 1997 Feb;18(1):26-45 PMID: 9034785
  32. The FGF family of growth factors and oncogenes.
    Adv Cancer Res. 1992;59:115-65 PMID: 1381547
  33. Formulation of a novel synthetic medium for selectively culturing rat CNS neurons.
    Brain Res. 1985 Oct;354(2):219-27 PMID: 4052813
  34. Tumour-derived exosomes or microvesicles: another mechanism of tumour escape from the host immune system?
    Br J Cancer. 2005 Jan 31;92(2):209-11 PMID: 15702078
  35. Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation.
    J Biol Chem. 2002 Feb 22;277(8):6667-75 PMID: 11741921
  36. Permeability properties of a three-cell type in vitro model of blood-brain barrier.
    J Cell Mol Med. 2005 Apr-Jun;9(2):373-9 PMID: 15963256
  37. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.
    J Immunol. 2001 Jun 15;166(12):7309-18 PMID: 11390481
  38. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device.
    J Cell Sci. 2000 Oct;113 Pt 19:3365-74 PMID: 10984428
  39. Shed membrane vesicles and clustering of membrane-bound proteolytic enzymes.
    Curr Top Dev Biol. 2003;54:411-32 PMID: 12696758
  40. Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH.
    Neoplasia. 2006 Feb;8(2):96-103 PMID: 16611402
  41. Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS.
    J Neurosci. 1999 Oct 1;19(19):8487-97 PMID: 10493749
Article Info
Journal
Journal of cellular and molecular medicine
Abbr.
J Cell Mol Med
ISSN
1582-1838
DOI
10.1111/j.1582-4934.2007.00100.x
Published
2007-00-00
Pages
1384-94
Language
English
Region
England
NLM ID
101083777
PMCID
PMC4401300
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1582-4934.2007.00100.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2