Open Access
Angiogenic signaling aberrantly induced by tumor hypoxia
Keizo Takenaga1
Department of Life Science, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo 693-8501, Japan.
DOI: 10.2741/3674 Volume 16 Issue 1, pp.31-48
Published: 01 January 2011

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.

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Keizo Takenaga. Angiogenic signaling aberrantly induced by tumor hypoxia. Frontiers in Bioscience-Landmark. 2011. 16(1); 31-48.