title: 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.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan. mfuruya@yokohama-cu.ac.jp
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A