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

Mediators of Inflammation
Carolina Cubillos-ZapataEduardo López-Collazo

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 HIF1α expression under IH. Moreover, these cells under IH polarize toward a tumor-promoting phenotype in a HIF1α-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 in vitro model as a result of the increased HIF1α secretion. Adequate oxygen restoration both in vivo (under continuous positive airway pressure treatment, CPAP) and in vitro 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.

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Citations

Jul 25, 2019·American Journal of Respiratory and Critical Care Medicine·Miguel Angel Martinez-GarciaDavid Gozal
Mar 19, 2020·International Journal of Molecular Sciences·Begoña Alburquerque-GonzálezPablo Conesa-Zamora
Sep 15, 2020·Oncoimmunology·Luis Augusto AguirreEduardo López-Collazo
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Aug 8, 2021·Cancers·Elena Díaz-GarcíaCarolina Cubillos-Zapata

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Methods Mentioned

BETA
flow cytometry
transfection

Software Mentioned

Prism

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