Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function

Wu, Soon‐Yi; Xing, Fei; Sharma, Sambad; Wu, Kerui; Tyagi, Abhishek; Yin, Lifang; Zhao, Dan; Deshpande, Ravindra Pramod; Shiozawa, Yusuke; Ahmed, Tamjeed; Zhang, Wei; Chan, Michael D.; Ruiz, Jimmy; Lycan, Thomas; Dothard, Andrew; Watabe, Kounosuke

doi:10.1084/jem.20191131

Cited by 73 publications

(70 citation statements)

References 81 publications

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“…Additionally, previous studies suggested that DNA damaging factors like smoking history and nicotine consumption could suppress innate immune function and promote lung cancer brain metastasis. 51 , 52 However, our results showed no difference in the proportion of distant metastasis between high and low EXO1 expression groups in our cohort, possibly due to the small size of cases. Interestingly, as an outstanding enriched pathway in KEGG, neuroactive ligand-receptor interaction was reported to be closely related to smoking-induced lung cancers.…”

Section: Discussioncontrasting

confidence: 64%

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma

Zhou¹,

Feng²,

Chen³

et al. 2021

OTT

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Background Exonuclease 1 (EXO1) has been identified to be highly expressed in different human malignancies, but its expression and prognostic role in lung adenocarcinoma (LUAD) remain unknown. Materials and Methods Two independent cohorts extracted from public databases and one cohort from our center were analyzed in this study. Expression levels of EXO1 in LUAD tissues and paired para-cancer tissues were detected. The prognostic value of EXO1 in LUAD patients was evaluated in the three cohorts. Enrichment analyses were performed to explore the possible underlying biological pathways. Moreover, we also explored the correlations between EXO1 and tumor-infiltrating immune cells and evaluated the impact of EXO1 knock-down on the migration of lung cancer cells. Results In this study, we found that EXO1 was highly expressed in LUAD tissues compared with para-cancerous tissues in public databases ( p < 0.01), which was consistent with our data ( p < 0.01). Survival analysis indicated that high expression of EXO1 was associated with poor prognosis in LUAD ( p < 0.01). Enrichment analyses indicated that biological pathways like cell cycle regulation, DNA damage and repair, immune response, neuroactive ligand-receptor interaction, may be associated with EXO1 aberrant expression. Moreover, high expression of EXO1 was correlated with decreased infiltrating B cells ( p < 0.01) and CD4+ T cells ( p < 0.01) levels, and low infiltrating levels of B cells ( p < 0.01) and dendritic cells (DCs) ( p < 0.05) indicated poor overall survival (OS) in LUAD. Additionally, in vitro experiments suggested that knockdown of EXO1 may inhibit the migratory ability of lung cancer cells. Conclusion In conclusion, EXO1 is a potential prognostic biomarker in LUAD, and correlates with infiltrating levels of immune cells in the tumor microenvironment. Further prospective validation of EXO1 in lung cancer is warranted.

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Section: Discussioncontrasting

confidence: 64%

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma

Zhou¹,

Feng²,

Chen³

et al. 2021

OTT

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“…TAMs polarize towards M2 type through the IL-6/STAT3 signaling pathway to promote tumor metastasis and rejects immune cells from penetrating ( 108 – 110 ). Wu SY et al proved that M2 macrophages are closely related to brain metastasis of lung cancer ( 111 ). On the other hand, by regulating mTOR, TAMs block normal glycolysis, induce excessive angiogenesis, and form abnormal blood vessels ( 112 ).…”

Section: Mechanism Of Lung Cancer Driver Genes In Brain Metastasismentioning

confidence: 99%

Advances in Lung Cancer Driver Genes Associated With Brain Metastasis

Kang

Jin

et al. 2021

Front. Oncol.

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Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer.

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“…Despite the lack of carcinogenicity evidence, it has been reported that nicotine promotes tumour cell survival by decreasing apoptosis and increasing proliferation [ 49 ], indicating that it may work as a “tumour enhancer”. In a very recent study, chronic administration of nicotine to mice (1 mg/kg every 3 days for a 60-day period) enhanced brain metastasis by skewing the polarity of M2 microglia, which increases metastatic tumour growth [ 50 ]. Assuming that a conventional cigarette contains 0.172–1.702 mg of nicotine [ 51 ], the daily nicotine dose administered to these animals corresponds to 40–400 cigarettes for a 70 kg-adult, which is a dose of an extremely heavy smoker.…”

Section: Introductionmentioning

confidence: 99%

An updated overview of e-cigarette impact on human health

2021

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The electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).

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Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function

Cited by 73 publications

References 81 publications

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma

Advances in Lung Cancer Driver Genes Associated With Brain Metastasis

An updated overview of e-cigarette impact on human health

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