sE-cadherin and sVE-cadherin indicate active epithelial/endothelial to mesenchymal transition (EMT and EndoMT) in smokers and COPD: implications for new biomarkers and therapeutics

Eapen, Mathew Suji; Myers, Stephen; Lu, Wenying; Tanghe, Chloé; Sharma, Pawan; Sohal, Sukhwinder Singh

doi:10.1080/1354750x.2018.1479772

Cited by 17 publications

(14 citation statements)

References 29 publications

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“…These results were demonstrated in a dose-response manner with pack-years [95]. Since ANGPT-2 was secreted by vascular endothelial cells in Weibel-Palade bodies, vascular remodeling had also been widely reported in mild to severe cases of COPD [77, 96, 97]. These findings sustained the assumption that CS altered endothelial cell function in cigarette-associated COPD patients.…”

Section: Tissue Repair and Remodelingmentioning

confidence: 66%

Cigarette Smoke Induced Lung Barrier Dysfunction, EMT, and Tissue Remodeling: A Possible Link between COPD and Lung Cancer

Hou

et al. 2019

BioMed Research International

114

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Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide. The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes. These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease. A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer. In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent. In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression. The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death. Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks. Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer. In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer.

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Section: Tissue Repair and Remodelingmentioning

confidence: 66%

Cigarette Smoke Induced Lung Barrier Dysfunction, EMT, and Tissue Remodeling: A Possible Link between COPD and Lung Cancer

Hou

et al. 2019

BioMed Research International

114

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“…The deleterious effect of CSE on BBB integrity might be consistent with the occurrence of a biological process known as endothelial to mesenchymal transition (EndoMT). Similar to airway epithelial to mesenchymal transition (EMT), EndoMT is a complex process whereby endothelial cells lose their specific markers such as the adheren junction protein VE-cadherins 42,43 , which is important for maintaining BBB integrity. Under chronic oxidative damage and inflammation (notably TGF-β) EndoMT can be initiated 42,44 .…”

Section: Discussionmentioning

confidence: 99%

“…Similar to airway epithelial to mesenchymal transition (EMT), EndoMT is a complex process whereby endothelial cells lose their specific markers such as the adheren junction protein VE-cadherins 42,43 , which is important for maintaining BBB integrity. Under chronic oxidative damage and inflammation (notably TGF-β) EndoMT can be initiated 42,44 . EMT is an active process in smokers and COPD patients 45,46 .…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation

Bernard

Vlahos

et al. 2019

Sci Rep

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Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. In addition, cerebral endothelial dysfunction (particularly at the level of the blood-brain barrier [BBB]) contributes to stroke pathogenesis. Therefore, we hypothesized that cigarette smoking may influence stroke, at least in part, by exacerbating ischaemia-induced BBB disruption. To test this, we examined the effect of CSE on the permeability of cerebral endothelial cells exposed to oxygen glucose deprivation and reoxygenation (OGD + RO). We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE. Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were however markedly lower. Furthermore, this occurred in association with elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defence response. Lastly, we found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β). Collectively, these results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, however, this is not linked to elevated ROS levels but may involve inflammatory mechanisms.

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“…Similar to epithelial plasticity in EMT, endothelial cells can also lose markers such as vascular endothelial cadherin (VE-cadherin), can attain a motile phenotype and can express fibroblast associated markers such as vimentin, type I collagen, and α-smooth muscle actin (SMA) [239].…”

Section: Endothelial-to-mesenchymal Transition (Endomt)mentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Eapen

Hansbro

Larsson‐Callerfelt

et al. 2018

Drugs

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COPD and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking, and exert a considerable societal burden. People suffering from COPD are at a higher risk of developing lung cancer than those without COPD and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower post-operative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we shall provide a detailed overview of possible underlying factors that link COPD and lung cancer and current therapeutic advances from both human and pre-clinical animal models that can effectively mitigate this unholy relationship. Running head-COPD and lung cancer: understanding and treatments

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sE-cadherin and sVE-cadherin indicate active epithelial/endothelial to mesenchymal transition (EMT and EndoMT) in smokers and COPD: implications for new biomarkers and therapeutics

Cited by 17 publications

References 29 publications

Cigarette Smoke Induced Lung Barrier Dysfunction, EMT, and Tissue Remodeling: A Possible Link between COPD and Lung Cancer

Cigarette Smoke Induced Lung Barrier Dysfunction, EMT, and Tissue Remodeling: A Possible Link between COPD and Lung Cancer

Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

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