Journal article
Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis
Toxicological sciences, Vol.127(1), pp.42-53
05/2012
DOI: 10.1093/toxsci/kfs087
PMCID: PMC3327869
PMID: 22331491
Abstract
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.
Details
- Title: Subtitle
- Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis
- Creators
- Mei Xu - University of KentuckyGang Chen - University of KentuckyWei Fu - West Virginia UniversityMingjun Liao - University of KentuckyJacqueline A Frank - University of KentuckyKimberly A Bower - University of KentuckyShengyun Fang - University of Maryland, BaltimoreZhuo Zhang - University of KentuckyXianglin Shi - University of KentuckyJia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.127(1), pp.42-53
- Publisher
- Oxford University Press
- DOI
- 10.1093/toxsci/kfs087
- PMID
- 22331491
- PMCID
- PMC3327869
- ISSN
- 1096-6080
- eISSN
- 1096-0929
- Language
- English
- Date published
- 05/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984201119302771
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