MOLECULAR MECHANISMS OF DEVELOPMENTAL AND TUMOR ANGIOGENESIS

Angiogenesis, the sprouting of capillaries from preexisting vessels, i s of fundamental importance during embryonic development and is the pr incipal process by which the brain and certain other organs become vas cularized. Angiogenesis occurs during embryonic development but is alm ost absent in adult tissues. Transient and tightly controlled (physiol ogical) angiogenesis in adult tissues occurs during the female reprodu ctive cycle and during wound healing. In contrast, pathological angiog enesis is characterized by the persistent proliferation of endothelial cells, and is a prominent feature of diseases such as proliferative r etinopathy, rheumathoid arthritis, and psoriasis. In addition, many tu mors are able to attract blood vessels from neighbouring tissues. Tumo r-induced angiogenesis requires a constitutive activation of endotheli al cells. These endothelial cells dissolve their surrounding extracell ular matrix, migrate toward the tumor, proliferate, and form a new vas cular network, thus supplying the tumor with nutrients and oxygen and removing waste products. The onset of angiogenesis in human gliomas is characterized by the expression of genes encoding angiogenic growth f actors such as vascular endothelial growth factor (VEGF), platelet-der ived growth factor (PDGF) in tumor cells, and coordinate induction of genes in endothelial cells which encode the respective growth factor r eceptors. Developmental and tumor angiogenesis appear to be regulated by a paracrine mechanism involving VEGF and VEGF receptor-1 and -2.