Journal of Molecular Medicine

, Volume 86, Issue 7, pp 785–789

R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways

Review

DOI: 10.1007/s00109-008-0337-z

Cite this article as:
Cao, Y., Cao, R. & Hedlund, EM. J Mol Med (2008) 86: 785. doi:10.1007/s00109-008-0337-z

Abstract

In a fast-growing malignant tissue, tumor blood vessels are exposed to multiple growth factors and cytokines. Although the role of individual factors and their signaling pathways in regulation of tumor neovascularization is relatively well-studied, little is known about complex interactions between these factors and their cooperative effects in promoting tumor angiogenesis and metastasis. Our recent studies show that quiescent vascular endothelial cells usually remaining silence to platelet-derived growth factor (PDGF)-BB stimulation acquire their hyperresponsiveness after stimulation with fibroblast growth factor (FGF)-2, which transcriptionally switches on PDGF receptor expression in the activated endothelial cells. Interestingly, PDGF-BB also transduces positive feedback signals to the FGF-2 signaling system by amplifying its receptor expression in vascular mural cells. These uncoordinated reciprocal interactions in the tumor environment lead to the formation of disorganized and primitive vasculatures that facilitate tumor growth and metastasis in mice. These findings provide an example of complex interaction between tumor angiogenic factors. Thus, therapeutic development of antiangiogenic agents for the treatment of cancer should be aimed to block multiple angiogenic signaling pathways and their interactive loops.

Keywords

Angiogenesis Cancer Metastasis Growth factor Inhibitor 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell BiologyKarolinska InstituteStockholmSweden

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