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Comment
. 2003 May;111(9):1277-80.
doi: 10.1172/JCI18539.

Double target for tumor mass destruction

Pipsa Saharinen  1 , Kari Alitalo
Affiliations
Comment

Double target for tumor mass destruction

Pipsa Saharinen et al. J Clin Invest. 2003 May.
No abstract available

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Figures

Figure 1
Figure 1
Growth factor receptor signals involved in tumor angiogenesis and vascular development. A solid tumor is dependent on new blood vessels for growth. (a) Angiogenesis is induced by VEGF produced mainly by hypoxic tumor cells and inflammatory cells (such as macrophages, which also secrete MMPs involved in the angiogenic switch) (19). Placental growth factor (PlGF) produced in the tumor may recruit bone marrow–derived endothelial precursor cells (EPCs), which become incorporated into the angiogenic vessels (20). The tip cells of a growing angiogenic sprout, and also the tumor cells, secrete PDGF-B, which binds to the EC surface and recruits PCs to migrate along the angiogenic sprouts (8, 9). In normal tissues, blood vascular ECs and PCs are in tight contact, and angiopoietin-1 (Ang-1) increases the stability of the vessels (b). In tumor vessels, Ang-2, an antagonist of Ang-1, is produced by the ECs, and the PCs are often only loosely attached to EC tubes; they also have long projections reaching out from the vessels to the surrounding matrix (13, 22) (c). The tumor blood vessels are leaky and the peritumoral lymphatic vessels (shown in yellow in panel a) cannot clear the extravasated material (10), which results in increased interstitial fluid pressure (IFP) within the tumor. The findings of Bergers et al. now suggest that concomitant inhibition of ECs and PCs through inhibition of their respective transmembrane tyrosine kinase receptors VEGFR-2 and VEGFR-1 (d) and PDGFR-β (e) results in more efficient inhibition of angiogenesis (4). The roles of additional ligands, VEGF-B (23) and PDGF-D (24, 25), which bind to VEGFR-1 and PDGFR-β, respectively, are not yet clear in these processes.
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References

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