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Loss of Complement Factor H in Plasma Increases Endothelial Cell Migration.

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2017

J Cancer. 2017 Jul 15;8(12):2184-2190. doi: 10.7150/jca.19452. eCollection 2017.

Loss of Complement Factor H in Plasma Increases Endothelial Cell Migration.

J Liu;J Hoh

Shandong University, Jinan, Shandong, China. Yale University, New Haven, CT, USA.

Service type: Knockout mice

Abstract

Tumor growth depends on angiogenesis, the growth of new blood vessels. Complement factor H (CFH) is a plasma glycoprotein that functions as a regulator of the complement system. The aim of this study is to delineate the role of CFH in angiogenesis. A conditional null allele of the Cfh gene was generated in C57BL/6J mice by flanking the exon 3 with loxP sites. The Cfhflox/flox mice were crossed with Rosa26-Cre mice to obtain the mice homozygotes of Cfh deletion (Cfh-/-). The Cfh-/- mice were examined by in vivo angiogenesis assays. Mouse endothelial cells were treated with media containing 5% of mouse plasma from the wildtype or Cfh-/- mice and assayed for proliferation, viability and migration. The Cfh-/- mice did not display any obvious abnormalities. They demonstrated a pro-angiogenic phenotype in matrigel plug assay, but not in aorta ring assay. In vitro, loss of Cfh in plasma does not affect proliferation or viability, but significantly increases migration of mouse endothelial cells. Our findings suggest that plasma CFH inhibits angiogenesis by reduction of endothelial cell migration. Thus the mutation of CFH might lead to excessive tumor angiogenesis.

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