Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor

Zhang, Xiaobin; Yang, Yuyun; Zeng, Yiming; Zeng, Huiqing; Fu, Biqian; Ko, Chih‐Yuan; Luo, Xiangfeng; Du, Yanping; Chen, L.-D.; Lai, Yue‐Hua; Wu, Yang

doi:10.1007/s12094-018-1955-8

Cited by 18 publications

(24 citation statements)

References 36 publications

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“…Mice in the IH group were subjected to the IH environment. Exposure was performed according to our previous study (16), with some modification. Mice in the IH group were caged in a self-made plexiglass chamber with one-way valves.…”

Section: Ih Exposurementioning

confidence: 99%

Intermittent hypoxia enhances the tumor programmed death ligand 1 expression in a mouse model of sleep apnea

Huang¹,

Zhang²,

Wang³

et al. 2019

Ann. Transl. Med

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Background: As a hallmark of obstructive sleep apnea (OSA), intermittent hypoxia (IH) promotes tumor progress. The high expression of programmed death 1 and programmed death ligand 1 (PD-L1) in tumor leads to immune evasion and subsequently aggravates tumor progress. This study aims to determine the tumor PD-L1 expression under the IH condition.Methods: A total of 24 C57BL/6J mice were randomly assigned to the normoxia (control, CTL) group and the IH group. Mice in the IH group were subjected to the IH condition for 5 weeks. Lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Tumor PD-L1 expression was detected by immunohistochemistry (IHC). Correlation between tumor weight, tumor volume, and expression of PD-L1 was analyzed.Results: Compared to the CTL group, mice in the IH group had a high PD-L1 expression. The IH can enhance the tumor PD-L1 expression. Tumor weight, volume, and HIF-1α levels were closely associated with the PD-L1 expression in the IH group, while dissimilar findings were observed in the CTL group. Conclusions:The IH enhances tumor PD-L1 expression in OSA mimicking mice. Additional studies are required to clarify the underlying mechanism.

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Section: Ih Exposurementioning

confidence: 99%

Intermittent hypoxia enhances the tumor programmed death ligand 1 expression in a mouse model of sleep apnea

Huang¹,

Zhang²,

Wang³

et al. 2019

Ann. Transl. Med

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“…Therefore, our current knowledge of the pathophysiology of cancer and OSA provides biological plausibility to the hypothesis that this sleep breathing disorder can initiate and/or aggravate malignancies. [13,17,20,22,[25][26][27][29][30][31][32]43,44] 3 [16,24,28] ↑ 13/13 ↑ 13/13…”

Section: Introductionmentioning

confidence: 99%

Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?

Gozal

Almendros

Phipps

et al. 2020

IJMS

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Obstructive sleep apnoea (OSA) is a prevalent disorder associated with increased cardiovascular, metabolic and neurocognitive morbidity. Recently, an increasing number of basic, clinical and epidemiological reports have suggested that OSA may also increase the risk of cancer, and adversely impact cancer progression and outcomes. This hypothesis is convincingly supported by biological evidence linking certain solid tumours and hypoxia, as well as by experimental studies involving cell and animal models testing the effects of intermittent hypoxia and sleep fragmentation that characterize OSA. However, the clinical and epidemiological studies do not conclusively confirm that OSA adversely affects cancer, even if they hold true for specific cancers such as melanoma. It is likely that the inconclusive studies reflect that they were not specifically designed to test the hypothesis or because of the heterogeneity of the relationship of OSA with different cancer types or even sub-types. This review critically focusses on the extant basic, clinical, and epidemiological evidence while formulating proposed directions on how the field may move forward.

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“…Such changes appeared to be related to HIF-1α 8 . CIH increased VEGF expression and microvessel density in a mouse model of OSA 31 . CIH-induced alterations in tumor-associated macrophages (TAMs) were associated with adverse cancer outcomes in a mouse model of lung cancer 9 .…”

Section: Discussionmentioning

confidence: 89%

Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer

Kang

Kwon

Kim

et al. 2020

Sci Rep

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the purpose of this study was to evaluate whether obstructive sleep apnea (oSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VeGf) and metastasis-related matrix metalloproteinases (MMp) were measured. the expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-eRK were measured by western blot. the number (p < 0.01) and volume (p < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after iH exposure. ciH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth. Obstructive sleep apnea (OSA) is characterized by recurrent occlusion of the upper airway during sleep leading to chronic intermittent hypoxia (CIH). OSA is a highly prevalent sleep disorder affecting at least 3% to 7% of the adult population 1. OSA has been shown to be associated with morbidities including metabolic syndrome, systemic hypertension, pulmonary vascular disease, ischemic heart disease and congestive heart failure 2. In addition, OSA-related CIH has been suggested to affect tumor development and progression 3. OSA has been implicated in the increasing incidence of certain types of solid malignancies. In a Spanish cohort, increased overnight hypoxia as a surrogate of OSA severity was associated with increased cancer incidence in selected populations 4-6. Also, OSA was associated with increased cancer mortality in a community-based sample 7. The association between OSA and lung cancer has been evaluated. OSA-related CIH induced resistance to apoptosis and increased metastasis in lung cancer cells, in a manner related to hypoxia inducible factor 1α (HIF-1α) 8. The role of immune cells has been suggested as a potential mechanism linking OSA and cancer. Almendros et al. demonstrated that CIH induced changes in host immune responses are related to adverse cancer outcomes. CIH increases the mobilization of tumor-associated macrophages (TAMs) into tumors, and induces macrophages to transform from an anti-tumor phenotype (M1) to a tumor-promoting phenotype (M2) 9. Cyclooxygenase-2 inhibited IH-induced M2 polarization of TAMs and prevented IH-induced adverse tumor outcomes in a mouse model of sleep apnea 10. OSA-related CIH altered CD8 + T-cells in combination with changes in the tumor microenvironment that enhanced malignant tumor properties 11. Studies...

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Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor

Cited by 18 publications

References 36 publications

Intermittent hypoxia enhances the tumor programmed death ligand 1 expression in a mouse model of sleep apnea

Intermittent hypoxia enhances the tumor programmed death ligand 1 expression in a mouse model of sleep apnea

Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?

Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer

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