Role of hypoxia in tumor angiogenesis-molecular and cellular angiogenic crosstalk.
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.
Acker
Till
T
Department of Cell and Molecular Biology, Karolinska Institute, Box 285, SE-17177, Stockholm, Sweden. till.acker@cmb.ki.se
Plate
Karl H
KH
D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D042682:Angiopoietins; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors