Original Paper

Angiogenesis

, Volume 15, Issue 4, pp 745-760

Estrogen receptor alpha as a key target of organochlorines to promote angiogenesis

  • Nicolas ClereAffiliated withLUNAM UniversitéINSERM UMR 1063, Université d’Angers, PBH-IRIS
  • , Emilie LauretAffiliated withLUNAM UniversitéINSERM UMR 1063, Université d’Angers, PBH-IRIS
  • , Yves MalthieryAffiliated withLUNAM UniversitéINSERM UMR 1063, Université d’Angers, PBH-IRIS
  • , Ramaroson AndriantsitohainaAffiliated withLUNAM UniversitéINSERM UMR 1063, Université d’Angers, PBH-IRIS Email author 
  • , Sébastien FaureAffiliated withLUNAM UniversitéINSERM UMR 1063, Université d’Angers, PBH-IRIS

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Epidemiological studies report that exposure to pesticides like chlordecone and lindane increases risk of cancer. They may act as endocrine disruptors via the activation of estrogen receptor α (ERα). Carcinogenesis involved angiogenesis and no available data regarding these organochlorines have been reported. The present study aimed at investigating the effects of lindane and chlordecone on cellular processes leading to angiogenesis through an involvement of ERα. Angiogenesis has been analyzed both in vitro, on human endothelial cells, and in vivo by quantifying neovascularization with the use of ECMgel® plug in mice. Both pesticides increased endothelial cell proliferation, migration and MMP2 activity. These toxics potentiated cell adhesion by enhancing FAK phosphorylation and stress fibers. The two organochlorines increased nitric oxide production via an enhancement of eNOS activity without modification of oxidative stress. Evidence has been provided that the two toxins increased in vivo neovascularization. Most interestingly, all the above processes were either partially or completely prevented after silencing of ERα. Altogether, these data highlight that organochlorines modulate cellular angiogenic processes through activation of ERα. This study further reinforces the harmful effects of these pesticides in carcinogenesis, particularly in the modulation of angiogenesis, a critical step in tumor promotion, through ERα.

Keywords

Endothelial cell Lindane Chlordecone Pro-angiogenic effects Estrogen receptor alpha