David Zagzag, MD, PhD

Blood vessels are constructed by two processes: vasculogenesis, whereby a primitive vascular network is established from multipotential mesenchymal progenitors, and angiogenesis, in which preexisting vessels (both in embryo and adult) send out capillary sprouts to produce new vessels. Angiogenesis and vasculogenesis as previously defined, are crucial process in both neural embryogenesis and neoplasia. Several angiogenic and vasculogenic factors and extracellular matrix (ECM) proteins have been implicated in the development and maturation of the central nervous system (CNS) and in the biology of brain tumors. The interaction between ECM components and these factors plays an important role in every step of the angiogenic and vasculogenic cascades. Our interest is in elucidating the expression patterns, trigger mechanisms, pathophysiological and molecular mechanisms that are related to the expression of both vasculogenic and angiogenic factors and ECM proteins.

Recently, we have focused our investigations on an ECM molecule, tenascin (TN). TN is a large complex protein of the ECM which is expressed in developing brain, cartilage and mesenchyme and is re-expressed in tumors, wound healing and inflammation. It is believed to be important for several cellular processes including cell adhesion, migration, and proliferation. In contrast to the low levels of TN found in normal adult brain, enhanced expression occurs in CNS embryogenesis and human astrocytomas. In situ hybridization of astrocytomas detects strong staining for TN mRNA in vascular cells, especially in hyperplastic vessels, including those at the invasive edge of the tumors, but not in normal brain vessels.

Tie-1 and Tie-2, two receptor tyrosine kinases, and their ligands angiopoetins have recently been described and are critical for vasculogenesis. We are currently investigating how these might be implicated in brain neoplasms.