Tumor angiogenesis. Part I. Its Role in Determination of Tumor Behavior;Factors Regulating Angiogenesis

Overview

The tumor stroma gains increasing attention in recent years. Angiogenesis (AG) is defined asformation of new vessels from the endothelium of the preexisting vasculature. The vascular beddoes not only provide supply of nutrition factors and oxygen as well as elimination of metabolicwaste, but the neo-formed vessels represent also a gate for lymphogenous and hematogenousmetastatic spread of the tumor. For tumor growth beyond the size of several mm, AG must bestarted to form vascular supply of tumor cells. After the switch to angiogenic phenotype, thetumor starts to exhibit rapid, almost exponential growth.AG is a complex process, involving degradation of the basement membrane of preexisting vessel,proliferation of endothelial buds or solid strands towards the angiogenic stimulus, maturation ofendothelial cells with formation of a luminized capillary, connection of such capillaries withcreation of vascular loops, and finally formation of a functional vessel, surrounded by basementmembrane and pericytes. The most intensive AG is observed at the periphery of the tumor.AG is regulated by numerous angiogenic and anti-angiogenic factors, which can be synthesizedand released by tumor cells themselves, stromal elements, as well as inflammatory cells, namelymacrophages.The issues of regulation of AG and importance of AG for tumor growth, progression and metasta-sis are discussed.

Key words:
malignant neoplasms - tumor angiogenesis - VEGF/VPF - tumor stroma - metastasis -prognosis