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Cell and Tissue Research

, Volume 314, Issue 1, pp 145–155 | Cite as

Role of hypoxia in tumor angiogenesis—molecular and cellular angiogenic crosstalk

  • Till AckerEmail author
  • Karl H. Plate
Review

Abstract

The mechanisms by which tumors recruit their vasculature has been subject to intense investigations. The acquisition of a functional blood supply seems to be rate-limiting for the ability of a tumor to grow beyond a certain size and to metastasize to other sites. Accumulating evidence indicates that hypoxia and the key transcriptional system, HIF (hypoxia-inducible factor), are the major triggers for new blood vessel growth in malignant tumors. Although vessel growth and maturation are complex and highly coordinated processes requiring the sequential activation of a multitude of factors, there is a consensus that vascular endothelial growth factor and angiopoietin signaling represent crucial steps in tumor angiogenesis. Recent insights into cellular and molecular crosstalk suggest a model in which hypoxia, HIF, and several HIF target genes participate in the coordinated collaboration between tumor, endothelial, inflammatory/hematopoietic, and circulating endothelial precursor cells to enhance and promote tumor vascularization. A well-integrated understanding of this intricate microenvironment may offer new opportunities for therapeutic intervention.

Keywords

Hypoxia-inducible factor Hypoxia Angiogenesis Oxygen sensing Inflammation Hypoxia-inducible factor-prolyl hydroxylase 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Department of Cell and Molecular BiologyKarolinska InstituteStockholmSweden
  2. 2.Institute of Neurology (Edinger Institute)Johann-Wolfgang Goethe UniversityFrankfurtGermany

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