A role for VEGF as a negative regulator of pericyte function and vessel maturation

Joshua I. Greenberg, David J. Shields, Samuel G. Barillas, Lisette M. Acevedo, Eric Murphy, Jianhua Huang, Lea Scheppke, Christian Stockmann, Randall S. Johnson, Niren Angle and David A. Cheresh ()
Additional contact information
Joshua I. Greenberg: School of Medicine
David J. Shields: Department of Pathology and Moore’s UCSD Cancer Center,
Samuel G. Barillas: School of Medicine
Lisette M. Acevedo: Department of Pathology and Moore’s UCSD Cancer Center,
Eric Murphy: Department of Pathology and Moore’s UCSD Cancer Center,
Jianhua Huang: Department of Pathology and Moore’s UCSD Cancer Center,
Lea Scheppke: Department of Pathology and Moore’s UCSD Cancer Center,
Christian Stockmann: Section of Molecular Biology, University of California, San Diego, California 92093, USA
Randall S. Johnson: Section of Molecular Biology, University of California, San Diego, California 92093, USA
Niren Angle: School of Medicine
David A. Cheresh: Department of Pathology and Moore’s UCSD Cancer Center,

Nature, 2008, vol. 456, issue 7223, 809-813

Abstract: Angoiogenesis and tumorigenesis: mixed messages from VEGF VEGF (vascular endothelial growth factor) is an important angiogenic factor that has been implicated in tumorigenesis. Two papers now show that the function of VEGF is far more complex, as VEFG can negatively regulate angiogenesis and limit tumorigenesis. In one study, Greenberg et al. found that VEGF can inhibit angiogenesis, by impeding the function of the PDGF (platelet-derived growth factor) receptor on pericytes, leading to a loss of pericyte coverage of blood vessels. This involves the formation of heterodimers between the receptors for VEGF and PDGF. In another paper, Stockmann et al. deleted VEGF production in myeloid cells, but not other cell types. Unexpectedly, they found more rapid tumour development in these mice, at the same time as attenuated tumour vascularization and the formation of morphologically and functionally normalized blood vessels. In contrast, tumours lacking VEGF altogether grew more slowly.

Date: 2008
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DOI: 10.1038/nature07424

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