Tenascin-C expression by angiogenic vessels in human astrocytomas and by 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 investigated the expression of TN protein and mRNA in nine astrocytomas. Immunogold 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 immunohistochemical findings. In situ hybridization of astrocytomas using a digoxigenin-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 detected with the sense probe. Moreover, we investigated the ability of human brain microvessel endothelial cells (HBMECs) in primary culture to synthesize TN in vitro. Western blot analysis of the culture supernatants from HBMECs detected large amounts of TN. Immunogold silver staining demonstrated the presence of TN on the surface of HBMECs and in the subendothelial matrix. The distribution of TN mRNA in vascular cells of astrocytomas and the ability of HBMECs to synthesize TN in vitro demonstrate that vascular cells, including endothelial cells, are a major source of TN associated with angiogenesis. Furthermore, our results suggest that TN expression may be associated with endothelial cell activation and may play an important role in angiogenesis.
Department of Pathology, New York University Medical Center, New York 10016, USA.
D
D
Zagzag
D R
DR
Friedlander
J
J
Dosik
S
S
Chikramane
W
W
Chan
M A
MA
Greco
J C
JC
Allen
K
K
Dorovini-Zis
M
M
Grumet
D001254:Astrocytoma / Q000098:blood supply / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D019063:Tenascin / Q000096:biosynthesis*
D012333:RNA, Messenger; D019063:Tenascin