ETS-1 converts endothelial cells to the angiogenic phenotype by inducing the expression of matrix metalloproteinases and integrin beta3

J Cell Physiol. 1999 Feb;178(2):121-32. doi: 10.1002/(SICI)1097-4652(199902)178:2<121::AID-JCP1>3.0.CO;2-F.

Abstract

The transcription factor ETS-1 is induced in endothelial cells (ECs) by angiogenic growth factors and the specific elimination of ETS-1 synthesis by antisense oligodeoxynucleotide inhibited angiogenesis in vitro (Iwasaka et al., 1996, J Cell Physiol 169:522-531). To understand the precise role of ETS-1 in angiogenesis, we established both high and low ETS-1 expression EC lines and compared angiogenic properties of these cell lines with those of the parental murine EC line, MSS-31. Although growth rate was almost identical for each cell line, the invasiveness was markedly enhanced in high ETS-1 expression cells and reduced in low ETS-1 expression cells compared with that of parental cells. The gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) and gelatinolytic activity of MMP-9 were significantly increased in high ETS-1 expression cells. Low ETS-1 expression cells could not spread on a vitronectin substratum, and the phosphorylation of focal adhesion kinase was markedly impaired because of the reduced expression of integrin beta3. These results indicate that ETS-1 is a principal regulator that converts ECs to the angiogenic phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Animals
  • Antigens, CD / genetics*
  • Base Sequence
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Division
  • Cell Line
  • Collagenases / genetics
  • DNA Primers / genetics
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression
  • Integrin beta3
  • Integrins / genetics
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / genetics*
  • Mice
  • Neovascularization, Physiologic*
  • Phenotype
  • Platelet Membrane Glycoproteins / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets
  • Receptors, Vitronectin / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vinculin / metabolism

Substances

  • Actins
  • Antigens, CD
  • Cell Adhesion Molecules
  • DNA Primers
  • Ets1 protein, mouse
  • Integrin beta3
  • Integrins
  • Platelet Membrane Glycoproteins
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Vitronectin
  • Transcription Factors
  • integrin alphaVbeta5
  • Vinculin
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse
  • Collagenases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1