Cycling hypoxia: A key feature of the tumor microenvironment

Michiels, Carine; Tellier, Céline; Feron, Olivier

doi:10.1016/j.bbcan.2016.06.004

Cited by 177 publications

(190 citation statements)

References 87 publications

(130 reference statements)

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“…Decreased expression of PHD3 was identified to be associated with poor differentiation and large tumor size. To date, numerous studies have revealed that PHD3 is associated with a favorable prognosis (15)(16)(17)(18)(19)22,24). For instance, Peurala et al (15) assessed the IHC expression of PHD3 in 102 breast cancer samples and revealed that the decreased expression of PHD3 correlates with poor differentiation, high proliferation and large tumor size.…”

Section: Discussionmentioning

confidence: 99%

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Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

et al. 2017

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Abstract. Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P= 0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

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Section: Discussionmentioning

confidence: 99%

“…However, these studies were performed in vitro under normal oxygen conditions. It is well established that cancer is a chronic hypoxic process (16). The present study aimed to explore the association between PHD3 and HIF2α expression in HCC (under hypoxic conditions).…”

Section: Introductionmentioning

confidence: 99%

Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

et al. 2017

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“…These unstable gradients can result in the unpredictable regulation of oxygen-sensitive transcriptional pathways, such as the HIF pathway 63,64 . Notably, the range of patterns of hypoxic exposure that may be found in pathological immunological niches is likely wide.…”

Section: Niche Features That Shape the Hif Responsementioning

confidence: 99%

Regulation of immunity and inflammation by hypoxia in immunological niches

2017

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Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

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“…Low vascular density and extensive hypoxia within the tumor indicates poor response to radiotherapy because that poor vascularity leads to inadequate uptake of chemotherapeutic agents and low supply of oxygen. 1,2 According to previous studies, 3Y5 the distribution of tumor vessel within the tumor is heterogeneous, and vasculature at tumor margin is more abundant. Compared with vasculature in the central region, vasculature at tumor margin plays a more important role in tumor growth and metastasis, and thus more closely associated with prognosis of tumor.…”

mentioning

confidence: 96%