Ethanol disrupts vascular endothelial barrier: Implication in cancer metastasis

Mei Xu, Gang Chen, Wei Fu, Mingjun Liao, Jacqueline A. Frank, Kimberly A. Bower, Shengyun Fang, Zhuo Zhang, Xianglin Shi, Jia Luo

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Both epidemiological and experimental studies indicate that ethanol exposure enhances tumor progression. Ethanol exposure promotes cancer cell invasion and is implicated in tumor metastasis. Metastasis consists of multiple processes involving intravasation and extravasation of cancer cells across the blood vessel walls. The integrity of the vascular endothelial barrier that lines the inner surface of blood vessels plays a critical role in cancer cell intravasation/extravasation. We examined the effects of ethanol on the endothelial integrity in vitro. Ethanol at physiologically relevant concentrations did not alter cell viability but disrupted the endothelial monolayer integrity, which was evident by a decrease in the electric resistance and the appearance of intercellular gaps in the endothelial monolayer. The effect of ethanol was reversible once ethanol was removed. The disruption of the endothelial monolayer integrity was associated with an increased invasion of cancer cells through the endothelial monolayer. Ethanol induced the formation of stress fibers; stabilization of actin filaments by jasplakinolide prevented ethanol-induced disruption of endothelial integrity and cancer cell invasion. VE-cadherin is a critical component of the adherens junctions, which regulates vascular endothelial integrity. Ethanol induced the endocytosis of VE-cadherin and the effect was blocked by jasplakinolide. Our results indicate that ethanol may facilitate cancer metastasis by disrupting the vascular endothelial barrier.

Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalToxicological Sciences
Issue number1
StatePublished - May 2012


  • Adherens junctions
  • Alcohol
  • Carcinogenesis
  • Invasion
  • Migration
  • Stress fibers

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Ethanol disrupts vascular endothelial barrier: Implication in cancer metastasis'. Together they form a unique fingerprint.

Cite this