Complexity of tumor vasculature and molecular targeting therapies.

Abstract

Malignant solid tumors require blood supply for their uncontrollable progression. Angiogenic blood vessels generally sprout from preexisting vascular cells. In addition, various types of precursor cells also participate in tumor neovascularization. They include endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells that are stimulated and attracted into tumor lesion, in which a wide variety of proinflammatory factors are involved. Among key molecules, vascular endothelial growth factor (VEGF) works as a mastermind regulator. Humanized monoclonal antibodies targeting VEGF-mediated signaling pathways are currently used as the most pervasive drugs in several types of progressive tumors. Adverse effects of these drugs include hypertension and proteinuria. Such symptoms are widely observed in preeclamptic patients whose blood contain high amount of natural VEGF antagonist. Vasoactive G protein-coupled receptors (GPCRs)-mediated signalings such as renin-angiotensin system and chemokine axes are also noticed that they may become effective therapeutic targets. In this review, we discuss general view of angiogenic microenvironment in solid tumors, and highlight several key signaling molecules and inhibitory effects of them on the whole system.

• Authors: Mitsuko Furuya, Kiyotaka Nagahama, Akihiro Ishizu, Noriyuki Otsuka, Yoji Nagashima, Ichiro Aoki
• Journal: Frontiers in bioscience (Elite edition) (Front Biosci (Elite Ed)) Vol. 3 Issue 2 Pg. 549-61 (01 01 2011) ISSN: 1945-0508 [Electronic] Singapore
• PMID: 21196334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies, Monoclonal
• Receptors, G-Protein-Coupled
• Vascular Endothelial Growth Factor A

Topics

• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Endothelial Cells (metabolism, physiology)
• Humans
• Neoplasms (blood supply, drug therapy)
• Neovascularization, Pathologic (drug therapy, physiopathology)
• Receptors, G-Protein-Coupled (metabolism)
• Signal Transduction (drug effects, physiology)
• Stem Cells (metabolism, physiology)
• Vascular Endothelial Growth Factor A (metabolism)