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

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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.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Karolinska Institute, Box 285, SE-17177, Stockholm, Sweden

    Till Acker

  2. Institute of Neurology (Edinger Institute), Johann-Wolfgang Goethe University, 60528, Frankfurt, Germany

    Till Acker & Karl H. Plate

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  1. Till Acker
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  2. Karl H. Plate
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Correspondence to Till Acker.

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The authors acknowledge grants from the Deutsche Krebshilfe (Dr. Mildred-Scheel Stiftung), the Bundesministerium für Bildung und Forschung (01KV0102), and the Deutsche Forschungsgemeinschaft (PL158/3–1, PL158/4–1 and PL158/4–2)

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Acker, T., Plate, K.H. Role of hypoxia in tumor angiogenesis—molecular and cellular angiogenic crosstalk. Cell Tissue Res 314, 145–155 (2003). https://doi.org/10.1007/s00441-003-0763-8

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