Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

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

doi:10.1093/toxsci/kfs087

Cited by 28 publications

(31 citation statements)

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“…The images of immunoblots were documented using Gel Logic 2200 Pro (Carestream Health, Rochester, NY). The intensity of specific proteins was quantified using Carestream Molecular Image Software as previously described (Xu et al 2012). …”

Section: Methodsmentioning

confidence: 99%

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy

et al. 2013

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Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system (CNS) neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1% oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al., 2010). We therefore hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1% oxygen) for 8 hours significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 hrs) was 49 ± 6% of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7% of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways.

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Section: Methodsmentioning

confidence: 99%

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy

et al. 2013

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“…Alcohol-induced disruption of endothelial integrity is evident by the decrease of electric resistance across the endothelial monolayer and the appearance of an intercellular gap among endothelial cells [48]. The effect of alcohol is reversible once alcohol is removed.…”

Section: Alcohol-induced Aggressiveness Of Breast Cancermentioning

confidence: 99%

“…The disruption of the endothelial monolayer integrity was associated with an increased invasion of cancer cells through the endothelial monolayer. It appears the alcohol-induced disruption of endothelial integrity is caused by damaged adherens junctions resulting from the endocytosis of VE-cadherin [48]. The epithelial–mesenchymal transition (EMT) is a developmental program but also plays an important role in cancer progression and metastasis.…”

Section: Alcohol-induced Aggressiveness Of Breast Cancermentioning

confidence: 99%

“…We demonstrate that alcohol causes a reversible disruption of the endothelial barrier and an enhanced invasion of cancer cells through the endothelial monolayer [48]. Vascular endothelial cadherin (VE-cadherin), a major component of endothelial adherens junctions, plays many functional roles in regulating endothelial barrier integrity.…”

Section: Cellular and Molecular Mechanisms Underlying Alcohol-indumentioning

confidence: 99%

“…The stabilization of the cadherin/catenin complex maintains endothelial integrity and inhibits tumor cell intravasation and extravasation. We show that alcohol inhibits VE-cadherin/β-catenin association and disrupts the endothelial barrier [48]. Since ROS can cause phosphorylation of the VE-cadherin and thereby result in disassembly of VE-cadherin/catenin complex and the breakdown of intercellular connections [80–82], the effect of alcohol on endothelial integrity may be mediated by ROS production.…”

Section: Cellular and Molecular Mechanisms Underlying Alcohol-indumentioning

confidence: 99%

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Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer

Wang

Zhang

et al. 2017

Pharmacological Research

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Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility of cancer cells by inducing cytoskeleton reorganization and enhancing the cancer cell invasion by causing degradation and reconstruction of the extracellular matrix (ECM). Moreover, alcohol may promote the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impair endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis. Furthermore, alcohol may stimulate tumor angiogenesis through the activation of cytokines and chemokines which promotes tumor growth. Additionally, alcohol may increase the cancer stem cell population which affects neoplastic cell behavior, aggressiveness, and the therapeutic response. Alcohol can be metabolized in the mammary tissues and breast cancer cells which produces reactive oxygen species (ROS), causing oxidative stress. Recent studies suggest that the epidermal growth factor receptor (EGFR) family, particularly ErbB2 (a member of this family), is involved in alcohol-mediated tumor promotion. Breast cancer cells or mammary epithelial cells over-expressing ErbB2 are more sensitive to alcohol’s tumor promoting effects. There is considerable cross-talk between oxidative stress and EGFR/ErbB2 signaling. This review further discusses how the interaction between oxidative stress and EGFR/ErbB2 signaling contributes to the cellular and molecular events associated with breast cancer aggressiveness. We also discuss the potential therapeutic approaches for cancer patients who drink alcoholic beverages.

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The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow

Mansouri

Ahmed

Ahmad

et al. 2022

Adv Healthcare Materials

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Microfluidic tissue barrier models have emerged to address the lack of physiological fluid flow in conventional "open-well" Transwell-like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the key advantages of both conventional open-well and microfluidic systems. Here, a plug-and-play flow module is developed to introduce on-demand microfluidic flow capabilities to an open-well device that features a nanoporous membrane and live-cell imaging capabilities. The magnetic latching assembly of this design enables bi-directional reconfiguration and allows users to conduct an experiment in an open-well format with established protocols and then add or remove microfluidic capabilities as desired. This work also provides an experimentally-validated flow model to select flow conditions based on the experimental needs. As a proof-of-concept, flow-induced alignment of endothelial cells and the expression of shear-sensitive gene targets are demonstrated, and the different phases of neutrophil transmigration across a chemically stimulated endothelial monolayer under flow conditions are visualized. With these experimental capabilities, it is anticipated that both engineering and bioscience laboratories will adopt this reconfigurable design due to the compatibility with standard open-well protocols.

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Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

Cited by 28 publications

References 50 publications

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy

Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer

The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow

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