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Pericyte-derived MFG-E8 regulates pathologic angiogenesis

Sei-ichiro Motegi1, Wolfgang W Leitner, Michael Lu

  • 1Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20802-1908, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|July 9, 2011
PubMed
Abstract

Insights

Milk fat globule-epidermal growth factor 8 (MFG-E8) is crucial for pericyte function in angiogenesis. MFG-E8 targeting may offer new therapeutic strategies for angiogenesis-related diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Vascular Biology

Background:

  • Milk fat globule-epidermal growth factor 8 (MFG-E8), also known as lactadherin, is a secreted glycoprotein.
  • MFG-E8 has been linked to enhancing vascular endothelial growth factor-dependent angiogenesis.
  • The primary sources and mechanisms of MFG-E8 action in vivo are not fully understood.

Purpose of the Study:

  • To identify the main in vivo sources of MFG-E8.
  • To further investigate the role of MFG-E8 in regulating angiogenesis.

Main Methods:

  • Utilized knockout mice and anti-MFG-E8 antibodies to assess MFG-E8 function.
  • Investigated MFG-E8 localization in melanoma and retinopathy models.
  • Quantified MFG-E8 mRNA in pericytes and pericyte precursors.
  • Employed small interfering RNAs and short hairpin RNAs to inhibit MFG-E8 production.
  • Tested the effects of anti-MFG-E8 antibodies on cell migration and angiogenesis.

Main Results:

  • MFG-E8 was found to colocalize with pericytes, not endothelial cells, in tumors and retinas.
  • Pericytes and pericyte precursors expressing platelet-derived growth factor receptor β showed high MFG-E8 mRNA levels.
  • MFG-E8 knockout mice exhibited reduced tumor and retinopathy-associated angiogenesis with decreased pericyte coverage.
  • Inhibition of MFG-E8 production or action attenuated pericyte migration in vitro and pathological angiogenesis in vivo.

Conclusions:

  • MFG-E8 plays a significant role in the function of pericytes and pericyte precursors.
  • MFG-E8-targeted therapies warrant further investigation for potential clinical applications.

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