Angiogenic signaling aberrantly induced by tumor hypoxia

作者：Takenaga Keizo^*

来源：Frontiers in Bioscience, 2011, 16: 31-48.

DOI：10.2741/3674

• Hypoxia
• Hypoxia-Inducible Factor
• Tumor Angiogenesis
• Proangiogenic Factor
• Antiangiogenic Factor
• Bone Marrow-Derived Cells
• HIF inhibitor
• Review

Tumor growth, invasion and metastasis are largely dependent on the development of tumor vasculature. A great number of pro- and antiangiogenic molecules, have been identified. Bone marrow-derived cells are mobilized and recruited to angiogenic sites, by a variety of growth factors and cytokines, to promote angiogenesis and the formation of new blood vessels. The hypoxic microenvironment that is inevitably generated in solid tumors is a major contributor to tumor angiogenesis. Tumor hypoxia aberrantly modulates the expression of many potent pro- and antiangiogenic molecules, primarily through the action of heterodimeric transcription factors termed hypoxia-inducible factors, HIF-1 and HIF-2. The disruption of the balance between pro- and antiangiogenic activities eventually leads to a shift in balance to a more angiogenic state. These findings have provoked considerable interest in HIFs as attractive targets for cancer therapy. Consequently, the development of small molecule HIF inhibitors is currently moving ahead at a fast pace.

• 出版日期2011-1-1