Pathophysiology of tumor neovascularization

Abstract

Mitsuko Furuya1, Mariko Nishiyama2, Yoshitoshi Kasuya2, Sadao Kimura2, Hiroshi Ishikura11Departments of Molecular Pathology, and 2Biochemistry and Molecular Pharmacology, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumorderived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized.Keywords: neovascularization, angiogenesis, tumor, endothelial cell, pericyte, chemokine