缺氧(环境)
炎症
肿瘤微环境
血管生成
癌症研究
癌变
转录因子
CXCL1型
信号转导
活性氧
生物
化学
细胞生物学
免疫学
医学
癌症
内科学
趋化因子
生物化学
基因
氧气
有机化学
肿瘤细胞
作者
Jan Korbecki,Donata Simińska,Magdalena Gąssowska-Dobrowolska,Joanna Listos,Izabela Gutowska,Dariusz Chlubek,Irena Baranowska-Bosiacka
标识
DOI:10.3390/ijms221910701
摘要
Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, transient) hypoxia are two types of hypoxia occurring in malignant tumors. They are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and nuclear factor κB (NF-κB), which induce changes in gene expression. This paper discusses in detail the mechanisms of activation of these two transcription factors in chronic and cycling hypoxia and the crosstalk between both signaling pathways. In particular, it focuses on the importance of reactive oxygen species (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses the importance of hypoxia in the formation of chronic low-grade inflammation in cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, and COX-2 together with PGE2. These factors induce angiogenesis and recruit various cells into the tumor niche, including neutrophils and monocytes which, in the tumor, are transformed into tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that participate in tumorigenesis.
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