Neoangiogenesis in human astrocytomas: expression and functional role of angiopoietins and their cognate receptors.

Since the introduction of the concept of an "angiogenic switch" driving tumor growth and malignant progression by Judah Folkman in 1971, there have been numerous scientific reports confirming the central concept that tumor growth is angiogenesis dependent. Various angiogenic genes and gene products, from both neoplastic and normal tissues, have been isolated, purified, and cloned that contribute to the 'angiogenic switch'. Of these various molecules, two have been identified that act specifically on endothelial cells. First is Vascular Endothelial Growth Factor (VEGF), the cognate receptors of which are almost specifically expressed on endothelial cells. VEGF plays a crucial role in the development of the embryonic vasculature by providing differentiation and mitogenic signals to endothelial cells and their mesodermal precursors. Second are the Angiopoietins and their cognate receptor, Tie2. Angiopoietins are primarily involved in maturation of both embryonal and adult vasculature, with Angiopoietin 1 2 being naturally occurring agonists and antagonists of Tie2 respectively, indicating a very precise level of regulation in-vivo. In this review we summarize what is known of the biological role of Angiopoietins and Tie2, their interaction with VEGF in normal and tumor related angiogenesis, with emphasis on their functional consequence in the progression and growth of malignant human astrocytomas.