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阻塞性睡眠呼吸暂停单核细胞表现出高水平的血管内皮生长因子分泌,增强肿瘤进展。

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression.

机构信息

The Innate Immune Response Group, Tumor Immunology Lab, IdiPAZ, La Paz University Hospital, Madrid, Spain.

Center for Biomedical Research Network of Respiratory Diseases (CIBERES), Madrid, Spain.

出版信息

Mediators Inflamm. 2018 May 28;2018:7373921. doi: 10.1155/2018/7373921. eCollection 2018.

Abstract

Obstructive sleep apnea (OSA) is a syndrome characterized by repeated pauses in breathing induced by a partial or complete collapse of the upper airways during sleep. Intermittent hypoxia (IH), a hallmark characteristic of OSA, has been proposed to be a major determinant of cancer development, and patients with OSA are at a higher risk of tumors. Both OSA and healthy monocytes have been found to show enhanced HIF1 expression under IH. Moreover, these cells under IH polarize toward a tumor-promoting phenotype in a HIF1-dependent manner and influence tumor growth via vascular endothelial growth factor (VEGF). Monocytes from patients with OSA increased the tumor-induced microenvironment and exhibited an impaired cytotoxicity in a 3D tumor model as a result of the increased HIF1 secretion. Adequate oxygen restoration both (under continuous positive airway pressure treatment, CPAP) and leads the monocytes to revert the tumor-promoting phenotype, demonstrating the plasticity of the innate immune system and the oxygen recovery relevance in this context.

摘要

阻塞性睡眠呼吸暂停(OSA)是一种综合征,其特征是在上呼吸道部分或完全塌陷时,睡眠期间呼吸反复暂停。间歇性低氧(IH)是 OSA 的一个标志特征,据推测它是癌症发展的一个主要决定因素,并且 OSA 患者发生肿瘤的风险更高。已经发现,在 IH 下,OSA 和健康单核细胞均显示出增强的 HIF1 表达。此外,这些细胞在 IH 下以 HIF1 依赖的方式向促进肿瘤的表型极化,并通过血管内皮生长因子(VEGF)影响肿瘤生长。由于 HIF1 分泌增加,OSA 患者的单核细胞增加了肿瘤诱导的微环境,并在 3D 肿瘤模型中表现出受损的细胞毒性。适当的氧气恢复(通过持续气道正压通气治疗,CPAP)和(通过补充氧气)都会导致单核细胞恢复肿瘤抑制表型,这证明了先天免疫系统的可塑性以及在这种情况下氧气恢复的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea2/5994578/3381dac20691/MI2018-7373921.001.jpg

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