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Angiogenesis, or neovascularization, is a complex process leading to formation of new blood vessels from the pre-existing vascular network of the tissue. Angiogenesis plays a central role in various physiological and pathological conditions, including embryonic development, reproduction, inflammation and wound healing, infertility, heart diseases, ulcers, rheumatoid arthritis, diabetic blindness and cancer. It is a multistep process involving EC activation, basement membrane and extracellular matrix (ECM) degradation, EC proliferation, migration and differentiation, synthesis of new basement membrane and maturation of new blood vessels. Tumor vasculature is considered to be of an "immature" nature with series of structural abnormalities. There are reciprocal paracrine interactions between ECs, tumor cells, stroma and ECM. Angiogenesis plays a key role in transformation of normal to malignant cell, tumor progression and metastasis. It is similar to the metastatic process in that it requires EC attachment, proteolysis, and locomotion to proceed. A close relationship exists between the tumor and ECs invasiveness of the tissue. The switch to the angiogenic phenotype involves a change in the local equilibrium between positive and negative regulators of the growth of microvessels. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are positive regulators of angiogenesis. Intimate cross-talk exists among bFGF and the different members of the VEGF family during angiogenesis, lymphangiogenesis, and vasculogenesis. A substantial body of experimental evidence supports the hypothesis that angiogenesis and angiogenic factors may be strong prognostic and predictive factors in breast carcinoma. This article reviews the current knowledge on angiogenesis and its positive regulators: bFGF and VEGF. . |
