Endothelial cell adhesion to soluble vascular endothelial growth factor receptor-1 triggers a cell dynamic and angiogenic phenotype

Angela Orecchia, Amel Mettouchi, Paolo Uva, Glenn C. Simon, Diego Arcelli, Simona Avitabile, Gianluca Ragone, Guerrino Meneguzzi, Karl H. Pfenninger, Giovanna Zambruno, Cristina Maria Failla

Research output: Contribution to journalArticle

Abstract

The aim of this study was to identify the molecular signals produced in human endothelial cells (ECs) by the interaction of α5β1 integrin with soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) present in the extracellular matrix. We generated a gene expression profile of ECs adhering to sVEGFR-1 or to fibronectin, the classic extracellular matrix ligand for α5β1 integrin or in a nonadhering condition. Several biological pathways were differently modulated, 3 protein kinase C substrates [adducin, myristoylated alanine-rich protein kinase C substrate (MARCKS), and radixin] were differently expressed and phosphorylated when cells adhering to sVEGFR-1 were compared with those adhering to fibronectin. Rac1 activation and Gα13 protein involvement through the interaction with radixin were also detected after attachment to sVEGFR-1, and these responses depended on active VEGFR-2 signaling. On sVEGFR-1, ECs exhibited a motile phenotype that was consistent with the abundant presence of MARCKS, a stabilizer of dynamic adhesions. Moreover, ECs silenced for radixin expression no longer responded to the proangiogenic VEGFR-1-derived peptide 12. We propose that the presence of sVEGFR-1 in the EC microenvironment directs α5β1 integrin signaling to generate a dynamic, motile phenotype. Our findings also provide new insights into the mechanism of action of proangiogenic peptide 12, relevant to a therapeutic perspective.

Original languageEnglish
Pages (from-to)692-704
Number of pages13
JournalFASEB Journal
Volume28
Issue number2
DOIs
Publication statusPublished - 2014

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Vascular Endothelial Growth Factor Receptor-1
Cell adhesion
Endothelial cells
Cell Adhesion
Endothelial Cells
Phenotype
Integrins
Protein Kinase C
Fibronectins
Alanine
Extracellular Matrix
G12-G13 GTP-Binding Protein alpha Subunits
rac1 GTP-Binding Protein
Substrates
Cellular Microenvironment
Vascular Endothelial Growth Factor Receptor-2
Peptides
Transcriptome
Gene expression
Cell Communication

Keywords

  • Cell migration
  • Integrin α5β1
  • Vessel formation

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Endothelial cell adhesion to soluble vascular endothelial growth factor receptor-1 triggers a cell dynamic and angiogenic phenotype. / Orecchia, Angela; Mettouchi, Amel; Uva, Paolo; Simon, Glenn C.; Arcelli, Diego; Avitabile, Simona; Ragone, Gianluca; Meneguzzi, Guerrino; Pfenninger, Karl H.; Zambruno, Giovanna; Failla, Cristina Maria.

In: FASEB Journal, Vol. 28, No. 2, 2014, p. 692-704.

Research output: Contribution to journalArticle

Orecchia, A, Mettouchi, A, Uva, P, Simon, GC, Arcelli, D, Avitabile, S, Ragone, G, Meneguzzi, G, Pfenninger, KH, Zambruno, G & Failla, CM 2014, 'Endothelial cell adhesion to soluble vascular endothelial growth factor receptor-1 triggers a cell dynamic and angiogenic phenotype', FASEB Journal, vol. 28, no. 2, pp. 692-704. https://doi.org/10.1096/fj.12-225771
Orecchia, Angela ; Mettouchi, Amel ; Uva, Paolo ; Simon, Glenn C. ; Arcelli, Diego ; Avitabile, Simona ; Ragone, Gianluca ; Meneguzzi, Guerrino ; Pfenninger, Karl H. ; Zambruno, Giovanna ; Failla, Cristina Maria. / Endothelial cell adhesion to soluble vascular endothelial growth factor receptor-1 triggers a cell dynamic and angiogenic phenotype. In: FASEB Journal. 2014 ; Vol. 28, No. 2. pp. 692-704.
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