Fig. 2
From: Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Potential factors contributing to tumor hypoxia. Carcinogenic factors, such as drug, carcinogen, and microbiota dysbiosis, impair EC shape and function in the vascular system. TME is remodeled by tumor cells, stromal cells and stromal components (e.g., fibrin), resulting in vascular deformation due to pressure. High metabolism in cancer cells, such as increased nucleic acid synthesis and increased protein anabolism, leads to relative hypoxia. Dysregulated proliferation and alignment of vascular ECs result in the formation of non-functional blood vessels. With the increased distance between tumor cells and blood vessels, O2 diffusion decreases and leads to hypoxia
