TENASCIN-C EXPRESSION BY ANGIOGENIC VESSELS IN HUMAN ASTROCYTOMAS ANDBY HUMAN BRAIN ENDOTHELIAL-CELLS IN-VITRO

The expression of the extracellular matrix glycoprotein tenascin-C (TN ) is enhanced in human astrocytomas and correlates with angiogenesis, To determine whether vascular cells are able to synthesize TN, we inve stigated the expression of TN protein and mRNA in nine astrocytomas. I mmunogold electron microscopy in two glioblastomas multiforme detected the presence of TN in an extracellular perivascular location and to a lesser extent among tumor cells, confirming light microscopy immunohi stochemical findings. In situ hybridization of astrocytomas using a di goxigenin-labeled antisense riboprobe detected strong staining for TN mRNA in vascular cells, especially in hyperplastic vessels, including those at the invasive edge of the tumors but not in vessels of normal brains. We observed weaker staining in tumor cells indicating a higher level of TN mRNA in vascular than in tumor cells. No staining was det ected with the sense probe. Moreover, we investigated the ability of h uman brain microvessel endothelial cells (HBMECs) in primary culture t o synthesize TN ill vitro. Western blot analysis of the culture supern atants from HBMECs detected large amounts of TN. Immunogold silver sta ining demonstrated the presence of TN on the surface of HBMECs and in the subendothelial matrix. The distribution of TN mRNA in vascular cel ls of astrocytomas and the ability of HBMECs to synthesize TN in vitro demonstrate that vascular cells, including endothelial cells, are a m ajor source of TN associated with angiogenesis. Furthermore, our resul ts suggest that TN expression may be associated with endothelial cell activation and may play an important role in angiogenesis.