Journal Article

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 and Jia Luo

in Toxicological Sciences

Volume 127, issue 1, pages 42-53
Published in print May 2012 | ISSN: 1096-6080
Published online February 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs087
Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

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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.

Keywords: alcohol; adherens junctions; carcinogenesis; invasion; migration; stress fibers

Journal Article.  5892 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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