Microenvironmental control of gene expression: implications for tumor angiogenesis, progression, and metastasis

Low oxygen tension (hypoxia) is an important prognostic factor in cancer treatment because it affects tumor formation and malignant progression. Many genes governing these complex processes have been found to be oxygen regulated. This article reviews the present knowledge of hypoxia-inducible gene expression and how this affects angiogenesis, progression, and metastasis. Of particular importance are hypoxia-regulated transcription factors because they can modulate expression of countless different genes. Additional genes analyzed in some detail include those encoding angiogenic growth factors, factors controlling blood flow, and those involved in metastasis. Although hypoxia is generally perceived as a hindrance to cancer therapy, it is possibly exploitable because severe oxygen deficiency is tumor specific. Strategies aimed at using the presence of hypoxia in solid tumors include oxygen sensitive chemotherapy and gene therapy.