Tumor Angiogenesis Regulated by Gaseous Molecules in Tumor Microenvironment: Oxygen, pH, and Nitric Oxide

摘要: Hypoxia and acidosis are hallmarks of metabolic environment in solid tumors regulate expression vascular endothelial growth factor (VEGF), a key angiogenesis factor. We developed novel vivo microscopy technique to simultaneously measure VEGF promoter activity, pO2 pH. To monitor vivo, we engineered human glioma cells that express green fluorescent protein (GFP) under the control promoter. Tissue pH were determined by phosphorescence quenching ratio imaging microscopy, respectively. These techniques have allowed us show transcription brain is regulated tissue via distinct pathways. Nitric oxide (NO) multi functional gaseous molecule regulates various physiological functions. shown NO mediates vessel tone, blood flow, permeability leukocyte-endothelial interactions tumors. Furthermore, found synthase (eNOS) plays predominant role VEGF-induced using angiogenic gel model NOS deficient mice. findings resulting mechanistic insights regulation molecules significant implications for tumor detection treatment strategies.